TY  - CONF
AU  - Medić-Milijić, Nataša
AU  - Jovanić, Irena
AU  - Nedeljković, Milica
AU  - Spurnić, Igor
AU  - Milovanović, Zorka
AU  - Ademović, Nejla
AU  - Tanić, Nikola
AU  - Tanić, Nasta
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6409
AB  - Breast cancer is the most commonly occurring malignancy and the leading
cause of cancer-related death in women. Triple-negative breast cancer (TNBC) is
the most aggressive breast cancer subtype and is associated with high recurrence
rates, high incidence of distant metastases and poor overall survival. The aim of
this study was to investigate the role PD-L1 (Programmed Death-Ligand 1), EGFR
(Epidermal Growth Factor Receptor) and Androgen Receptor (AR) expression in
TNBC promotion, progression and response to therapy,
This is a retrospective analysis of 125 patients with triple-negative breast cancer
operated at the Institute of Oncology and Radiology of Serbia in the period
2009 to 2014. The expression of PD-L1, EGFR and AR wеre observed using the
immunohistochemical staining method. PD-L1 expression was determined using
the combined positive score (CPS), EGFR expression was determined using the
Allred scoring system with cut-off values: ≤4 and >4 (low/high expression) while
determining the expression status of AR involved a quantitative method based on
the percentage of nuclear expression of malignant cells of any intensity (cut-off value
for positive expression was ≥10%).
Elevated expression of PD-L1 significantly correlated with higher tumor grade
(p=0.0002), nuclear grade (p=0.0007) and loco-regional recurrence (p=0.0146).
Alone, it did not show any significant influence on survival (DFI or OS). Contrary
to this, the expression of AR showed an impact on DFI (Disease Free Interval,
p=0.0171). In addition, elevated AR expression significantly correlated with higher
tumor grade. Interestingly, the expression of PD-L1 and AR significantly correlated
(Spearman r -0.2747; 95% confidence interval -0.4339 to -0.09895: P (two-tailed)
0.0019) and we were able to make two groups of patients, those who had high simultaneous expression of both genes and those who had low expression. Our
results revealed that simultaneous high expression of PD-L1 and AR significantly
correlates with tumor grade (p=0.05), nuclear grade (p=o.0242) and metastases
(p=0.0497) and has significant impact on DFI (p=0.0191) and OS (overall survival)
(p=0.0471). Notably, the expression of Ki67 absolutely correlates with the expression
of PD-L1 and AR, has the same pattern of expression. Moreover, reduced expression
of EGFR contributes to metastases (p=0.0249) and worse OS (p=0.0127).
In conclusion, we believe that concurrent examination of PD-L1, AR, EGFR and
Ki67 protein expression may be more useful in predicting TNBC clinical course
than the analysis of single protein expression. Specifically, our results showed
that simultaneous high expression of PD-L1 and AR, followed by Ki67 expression
constitutes a ‘high risk’ profile of TNBC. Combining these results with our previous
findings on PTEN-reduced/PI3K-high/mTOR-high expression could be the
promising formula.
AB  - Рак дојке је најчешћи тип малигнитета и водећи узрок смрти од карцинома
код жена. Троструко негативни карцином дојке (ТНБЦ) је најагресивнији
његов подтип који се одликује високом стопом рецидива, учесталом појавом
удаљених метастаза, као и лошим утицајем на укупно преживљавање. Циљ
ове студије је био одређивање експресије PD-L1 (Programmed Death-Ligand
1), EGFR (Epidermal Growth Factor Receptor) и андроген рецептора (АР) код
пацијенткиња оболелих од ТНКД као и да се утврди да ли њихова измењена
експресија корелира са клиничким током болести, прогресијом болести и/или
одговором на примењену терапију.
Овом ретроспективном студијом обухваћено је 125 пацијенткиња оболелох
од троструко негативних карцинома дојке које су у периоду 2009. до 2014.
године оперисане у Институту за онкологију и радиологију Србије. Експресија
PD-L1, EGFR и AR је одређена имунохистохемијском методом бојења. Статус
експресије PD-L1 је одређен коришћењем комбинованог позитивног скора
(ЦПС), експресија EGFR је одређена коришћењем Allred scoring система са
граничним вредностима: ≤4 и >4 (ниска/висока експресија), док је одређивање
статуса експресије AR подразумевало квантитативну методу базирану на
проценту нуклеарне експресије малигних ћелија било ког интезитета (гранична
вредност за позитивну експресију била је ≥10%).
Ова студија је показала да је повећана експресија PD-L1 у значајној
корелерацији са вишим хистолошким градусом тумора (p=0,0002), нуклеарним градусом (p=0,0007) и са чешћом појавом локо-регионалних рецидива
(p=0,0146). Повећана експресија PD-L1 протеина нема значањијег утицаја на
дужину интервала без болести и на укупно преживљавање (DFI и ОS). Супротно
овоме, експресија АR је у асоцијацији са DFI (p=0,0171), и у корелацији је са
вишим градусом тумора. Утврђено је такође да постоји значајна повезаност у
симултаној експресији ова два протеина , PD-L1 и АR (Spearman р -0,2747; 95%
интервал поверења -0,4339 до -0,09895: P (двострано) 0,0019). Истовремено
јасно су дефинисане две групе пацијенткиња-са повишеном експресијом PD-L1
и АR и са смањеном експресијом ова два протеина и утврђено је да симултана
експресија корелира са градусом тумора (п=0,05), нуклеарним градусом
(p=0.0242) и учесталошћу појаве метастаза (p=0,0497). Истовремено, симултана
експресија утиче на DFI (p=0,0191) и OS (p=0,0471). Запажено је да експресија
Ki67 значајно корелира са експресијом PD-L1 и AR, као и да има исти образац
експресије, док смањена експресија EGFR доприноси чешћој појави метастаза
(p=0,0249) и краћем интервалу укупног преживљавања (p=0,0127).
Добијени резултати сугеришу да би истовремено испитивање експресије
протеина PD-L1, АR, ЕGFR и Ki67 могло бити корисније у предвиђању
клиничког тока ТНКД од појединачних анализа. Наши резултати су показали
да би група ТНКД ”високог ризика“ могла бити она са симултаном високом
експресијом PD-L1 и АR, праћена високом експресијом Ki67.
PB  - Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
T1  - Prognostic and clinical significance of PD-L1, EGFR and androgen receptor (AR) expression in triple-negative breast cancer (TBNC) patients
T1  - Прогностички и клинички значај експресије PD-L1, EGFR и андрогеног рецептора (АР) код пацијената са троструко негативним карциномом дојке (ТНКД)
SP  - 67
EP  - 70
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6409
ER  - 

@conference{
author = "Medić-Milijić, Nataša and Jovanić, Irena and Nedeljković, Milica and Spurnić, Igor and Milovanović, Zorka and Ademović, Nejla and Tanić, Nikola and Tanić, Nasta",
year = "2023",
abstract = "Breast cancer is the most commonly occurring malignancy and the leading
cause of cancer-related death in women. Triple-negative breast cancer (TNBC) is
the most aggressive breast cancer subtype and is associated with high recurrence
rates, high incidence of distant metastases and poor overall survival. The aim of
this study was to investigate the role PD-L1 (Programmed Death-Ligand 1), EGFR
(Epidermal Growth Factor Receptor) and Androgen Receptor (AR) expression in
TNBC promotion, progression and response to therapy,
This is a retrospective analysis of 125 patients with triple-negative breast cancer
operated at the Institute of Oncology and Radiology of Serbia in the period
2009 to 2014. The expression of PD-L1, EGFR and AR wеre observed using the
immunohistochemical staining method. PD-L1 expression was determined using
the combined positive score (CPS), EGFR expression was determined using the
Allred scoring system with cut-off values: ≤4 and >4 (low/high expression) while
determining the expression status of AR involved a quantitative method based on
the percentage of nuclear expression of malignant cells of any intensity (cut-off value
for positive expression was ≥10%).
Elevated expression of PD-L1 significantly correlated with higher tumor grade
(p=0.0002), nuclear grade (p=0.0007) and loco-regional recurrence (p=0.0146).
Alone, it did not show any significant influence on survival (DFI or OS). Contrary
to this, the expression of AR showed an impact on DFI (Disease Free Interval,
p=0.0171). In addition, elevated AR expression significantly correlated with higher
tumor grade. Interestingly, the expression of PD-L1 and AR significantly correlated
(Spearman r -0.2747; 95% confidence interval -0.4339 to -0.09895: P (two-tailed)
0.0019) and we were able to make two groups of patients, those who had high simultaneous expression of both genes and those who had low expression. Our
results revealed that simultaneous high expression of PD-L1 and AR significantly
correlates with tumor grade (p=0.05), nuclear grade (p=o.0242) and metastases
(p=0.0497) and has significant impact on DFI (p=0.0191) and OS (overall survival)
(p=0.0471). Notably, the expression of Ki67 absolutely correlates with the expression
of PD-L1 and AR, has the same pattern of expression. Moreover, reduced expression
of EGFR contributes to metastases (p=0.0249) and worse OS (p=0.0127).
In conclusion, we believe that concurrent examination of PD-L1, AR, EGFR and
Ki67 protein expression may be more useful in predicting TNBC clinical course
than the analysis of single protein expression. Specifically, our results showed
that simultaneous high expression of PD-L1 and AR, followed by Ki67 expression
constitutes a ‘high risk’ profile of TNBC. Combining these results with our previous
findings on PTEN-reduced/PI3K-high/mTOR-high expression could be the
promising formula., Рак дојке је најчешћи тип малигнитета и водећи узрок смрти од карцинома
код жена. Троструко негативни карцином дојке (ТНБЦ) је најагресивнији
његов подтип који се одликује високом стопом рецидива, учесталом појавом
удаљених метастаза, као и лошим утицајем на укупно преживљавање. Циљ
ове студије је био одређивање експресије PD-L1 (Programmed Death-Ligand
1), EGFR (Epidermal Growth Factor Receptor) и андроген рецептора (АР) код
пацијенткиња оболелих од ТНКД као и да се утврди да ли њихова измењена
експресија корелира са клиничким током болести, прогресијом болести и/или
одговором на примењену терапију.
Овом ретроспективном студијом обухваћено је 125 пацијенткиња оболелох
од троструко негативних карцинома дојке које су у периоду 2009. до 2014.
године оперисане у Институту за онкологију и радиологију Србије. Експресија
PD-L1, EGFR и AR је одређена имунохистохемијском методом бојења. Статус
експресије PD-L1 је одређен коришћењем комбинованог позитивног скора
(ЦПС), експресија EGFR је одређена коришћењем Allred scoring система са
граничним вредностима: ≤4 и >4 (ниска/висока експресија), док је одређивање
статуса експресије AR подразумевало квантитативну методу базирану на
проценту нуклеарне експресије малигних ћелија било ког интезитета (гранична
вредност за позитивну експресију била је ≥10%).
Ова студија је показала да је повећана експресија PD-L1 у значајној
корелерацији са вишим хистолошким градусом тумора (p=0,0002), нуклеарним градусом (p=0,0007) и са чешћом појавом локо-регионалних рецидива
(p=0,0146). Повећана експресија PD-L1 протеина нема значањијег утицаја на
дужину интервала без болести и на укупно преживљавање (DFI и ОS). Супротно
овоме, експресија АR је у асоцијацији са DFI (p=0,0171), и у корелацији је са
вишим градусом тумора. Утврђено је такође да постоји значајна повезаност у
симултаној експресији ова два протеина , PD-L1 и АR (Spearman р -0,2747; 95%
интервал поверења -0,4339 до -0,09895: P (двострано) 0,0019). Истовремено
јасно су дефинисане две групе пацијенткиња-са повишеном експресијом PD-L1
и АR и са смањеном експресијом ова два протеина и утврђено је да симултана
експресија корелира са градусом тумора (п=0,05), нуклеарним градусом
(p=0.0242) и учесталошћу појаве метастаза (p=0,0497). Истовремено, симултана
експресија утиче на DFI (p=0,0191) и OS (p=0,0471). Запажено је да експресија
Ki67 значајно корелира са експресијом PD-L1 и AR, као и да има исти образац
експресије, док смањена експресија EGFR доприноси чешћој појави метастаза
(p=0,0249) и краћем интервалу укупног преживљавања (p=0,0127).
Добијени резултати сугеришу да би истовремено испитивање експресије
протеина PD-L1, АR, ЕGFR и Ki67 могло бити корисније у предвиђању
клиничког тока ТНКД од појединачних анализа. Наши резултати су показали
да би група ТНКД ”високог ризика“ могла бити она са симултаном високом
експресијом PD-L1 и АR, праћена високом експресијом Ki67.",
publisher = "Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina",
title = "Prognostic and clinical significance of PD-L1, EGFR and androgen receptor (AR) expression in triple-negative breast cancer (TBNC) patients, Прогностички и клинички значај експресије PD-L1, EGFR и андрогеног рецептора (АР) код пацијената са троструко негативним карциномом дојке (ТНКД)",
pages = "67-70",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6409"
}

Medić-Milijić, N., Jovanić, I., Nedeljković, M., Spurnić, I., Milovanović, Z., Ademović, N., Tanić, N.,& Tanić, N.. (2023). Prognostic and clinical significance of PD-L1, EGFR and androgen receptor (AR) expression in triple-negative breast cancer (TBNC) patients. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 67-70.
https://hdl.handle.net/21.15107/rcub_ibiss_6409

Medić-Milijić N, Jovanić I, Nedeljković M, Spurnić I, Milovanović Z, Ademović N, Tanić N, Tanić N. Prognostic and clinical significance of PD-L1, EGFR and androgen receptor (AR) expression in triple-negative breast cancer (TBNC) patients. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina. 2023;:67-70.
https://hdl.handle.net/21.15107/rcub_ibiss_6409 .

Medić-Milijić, Nataša, Jovanić, Irena, Nedeljković, Milica, Spurnić, Igor, Milovanović, Zorka, Ademović, Nejla, Tanić, Nikola, Tanić, Nasta, "Prognostic and clinical significance of PD-L1, EGFR and androgen receptor (AR) expression in triple-negative breast cancer (TBNC) patients" in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina (2023):67-70,
https://hdl.handle.net/21.15107/rcub_ibiss_6409 .

TY  - CONF
AU  - Ademović, Nejla
AU  - Tanić, Nasta
AU  - Tomić, Tijana
AU  - Murganić, Blagoje
AU  - Milić, Marina
AU  - Tanić, Nikola
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6327
AB  - Introduction: Astrocytoma and glioblastoma are the most agressive type of brain tumor. Glioblastoma IDH wild-type is a primary tumor which develops de novo, while Astrocytoma IDH mutant progresses from lower grade tumors. They are characterized by high heterogeneity and resistance to therapy which develop as a consequence of accumulation of mutations that lead to genomic instability.
Methods: We analysed genomic instability in 66 patients with malign brain tumors using arbitrarily primed PCR as DNA profiling method. Comparing DNA profiles of tumor and normal (blood) tissues, we detected quantitative and qualitative differences. Quantitative differences are represented by different band intensities and correspond to chromosomal instability (CIN). Qualitative changes seen as band shifts represent microsatellite instability (MIN). We correlated frequencies of genomic instability with tumor gradus and histophatological data.
Results: In patients with Glioblastoma IDH wild-type, percentages of high total genomic instability, MIN and CIN were 65%, 32% and 57%, respectfully. In patients with Astrocytoma IDHmutant, percentages of high total genomic instability, MIN and CIN for gradus 3 were 45%, 36% and 72%, respectfully while they were 40%, 40% and 40%, for gradus 4. In patients with NOS (not otherwise specified glioblastoma) percentages are 50%, 50% and 70%, respectfully.
Conclusion: Our results show that Glioblastoma IDH wild-type and Astrocytoma IDH mutant gradus 3 have higher genomic instability, while it is lower in Astrocytoma IDH mutant gradus 4. These results are in line with evolutionary theory of origin of cancer. Genomic instability in NOS tumors could be used as a prognostic marker.
PB  - Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
C3  - Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
T1  - Detection of genomic instability in malignant brain tumors
SP  - 98
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6327
ER  - 

@conference{
author = "Ademović, Nejla and Tanić, Nasta and Tomić, Tijana and Murganić, Blagoje and Milić, Marina and Tanić, Nikola",
year = "2023",
abstract = "Introduction: Astrocytoma and glioblastoma are the most agressive type of brain tumor. Glioblastoma IDH wild-type is a primary tumor which develops de novo, while Astrocytoma IDH mutant progresses from lower grade tumors. They are characterized by high heterogeneity and resistance to therapy which develop as a consequence of accumulation of mutations that lead to genomic instability.
Methods: We analysed genomic instability in 66 patients with malign brain tumors using arbitrarily primed PCR as DNA profiling method. Comparing DNA profiles of tumor and normal (blood) tissues, we detected quantitative and qualitative differences. Quantitative differences are represented by different band intensities and correspond to chromosomal instability (CIN). Qualitative changes seen as band shifts represent microsatellite instability (MIN). We correlated frequencies of genomic instability with tumor gradus and histophatological data.
Results: In patients with Glioblastoma IDH wild-type, percentages of high total genomic instability, MIN and CIN were 65%, 32% and 57%, respectfully. In patients with Astrocytoma IDHmutant, percentages of high total genomic instability, MIN and CIN for gradus 3 were 45%, 36% and 72%, respectfully while they were 40%, 40% and 40%, for gradus 4. In patients with NOS (not otherwise specified glioblastoma) percentages are 50%, 50% and 70%, respectfully.
Conclusion: Our results show that Glioblastoma IDH wild-type and Astrocytoma IDH mutant gradus 3 have higher genomic instability, while it is lower in Astrocytoma IDH mutant gradus 4. These results are in line with evolutionary theory of origin of cancer. Genomic instability in NOS tumors could be used as a prognostic marker.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia",
title = "Detection of genomic instability in malignant brain tumors",
pages = "98",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6327"
}

Ademović, N., Tanić, N., Tomić, T., Murganić, B., Milić, M.,& Tanić, N.. (2023). Detection of genomic instability in malignant brain tumors. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade., 98.
https://hdl.handle.net/21.15107/rcub_ibiss_6327

Ademović N, Tanić N, Tomić T, Murganić B, Milić M, Tanić N. Detection of genomic instability in malignant brain tumors. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:98.
https://hdl.handle.net/21.15107/rcub_ibiss_6327 .

Ademović, Nejla, Tanić, Nasta, Tomić, Tijana, Murganić, Blagoje, Milić, Marina, Tanić, Nikola, "Detection of genomic instability in malignant brain tumors" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):98,
https://hdl.handle.net/21.15107/rcub_ibiss_6327 .

TY  - CONF
AU  - Ademović, Nejla
AU  - Tomić, Tijana
AU  - Tanić, Nasta
AU  - Milić, Marina
AU  - Rakić, Miodrag
AU  - Tanić, Nikola
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6234
AB  - Introduction. Glioblastoma and Astrocytoma are diffuse malignant brain tumors and characterized as the most aggressive and invasive brain cancers. Glioblastoma IDH wild-type is a primary brain tumour that develops de novo, and Astrocytoma IDH mutant is a secondary tumour which arises by progression from lower tumour grades. They are characterized by poor survival, resistance to therapy and poor prognosis which develops as a consequence of genomic instability. Genomic instability also contributes to tumour heterogeneity and provides the genomic diversity necessary for selection.
Materials and methods. 31 patients with Glioblastoma IDH wild-type and Astrocytoma IDH mutant, grade 3 and 4, were analysed for the presence of genomic instability using AP-PCR, DNA profiling method. Comparing DNA profiles between tumour tissue and normal tissue (blood) of the same patient, we detected qualitative and quantitative changes. Qualitative changes are detected as the presence and absence of bands and are the manifestation of microsatellite instability (MIN). Quantitative changes are the representation of chromosomal instability (CIN) and are detected as differences in the intensity of bands. Survival analyses were performed using Kaplan & Maier test for survival data in relation to different histological tumour type and genomic instability. Statistical differences were considered significant for p≤ 0,05.
Results. Patients with Glioblastoma IDH wild-type have significantly shorter survival compared to other histological types (p=0,025). For each histological type that we analysed and each type of instability, MIN, CIN and total genomic instability, two groups of patients were made - those with high and low instability. Patients with Glioblastoma IDH wild-type that have low total genomic instability have significantly shorter survival (p=0,045) compared to other analysed types of brain cancer. Patients with Astrocytoma IDH mutant grade 4 who have high total genomic instability and high CIN have significantly shorter survival (p=0,018, p=0,007 respectfully).
Conclusion. Patients with Glioblastoma IDH wild-type have shorter survival which makes this tumour the most aggressive and malignat of all analysed tumours. Our results show that low genomic instability in Glioblastoma IDH wild-type and high genomic instability lead by high CIN in Astrocytoma IDH mutant, gradus 4 contribute to shorter survival, which makes genomic instability a potential good prognostic marker.
PB  - Belgrade, Serbia: Serbian Associaton for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - Genomic instability as a prognostic marker in malignant brain cancer
SP  - 90
EP  - 91
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6234
ER  - 

@conference{
author = "Ademović, Nejla and Tomić, Tijana and Tanić, Nasta and Milić, Marina and Rakić, Miodrag and Tanić, Nikola",
year = "2023",
abstract = "Introduction. Glioblastoma and Astrocytoma are diffuse malignant brain tumors and characterized as the most aggressive and invasive brain cancers. Glioblastoma IDH wild-type is a primary brain tumour that develops de novo, and Astrocytoma IDH mutant is a secondary tumour which arises by progression from lower tumour grades. They are characterized by poor survival, resistance to therapy and poor prognosis which develops as a consequence of genomic instability. Genomic instability also contributes to tumour heterogeneity and provides the genomic diversity necessary for selection.
Materials and methods. 31 patients with Glioblastoma IDH wild-type and Astrocytoma IDH mutant, grade 3 and 4, were analysed for the presence of genomic instability using AP-PCR, DNA profiling method. Comparing DNA profiles between tumour tissue and normal tissue (blood) of the same patient, we detected qualitative and quantitative changes. Qualitative changes are detected as the presence and absence of bands and are the manifestation of microsatellite instability (MIN). Quantitative changes are the representation of chromosomal instability (CIN) and are detected as differences in the intensity of bands. Survival analyses were performed using Kaplan & Maier test for survival data in relation to different histological tumour type and genomic instability. Statistical differences were considered significant for p≤ 0,05.
Results. Patients with Glioblastoma IDH wild-type have significantly shorter survival compared to other histological types (p=0,025). For each histological type that we analysed and each type of instability, MIN, CIN and total genomic instability, two groups of patients were made - those with high and low instability. Patients with Glioblastoma IDH wild-type that have low total genomic instability have significantly shorter survival (p=0,045) compared to other analysed types of brain cancer. Patients with Astrocytoma IDH mutant grade 4 who have high total genomic instability and high CIN have significantly shorter survival (p=0,018, p=0,007 respectfully).
Conclusion. Patients with Glioblastoma IDH wild-type have shorter survival which makes this tumour the most aggressive and malignat of all analysed tumours. Our results show that low genomic instability in Glioblastoma IDH wild-type and high genomic instability lead by high CIN in Astrocytoma IDH mutant, gradus 4 contribute to shorter survival, which makes genomic instability a potential good prognostic marker.",
publisher = "Belgrade, Serbia: Serbian Associaton for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "Genomic instability as a prognostic marker in malignant brain cancer",
pages = "90-91",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6234"
}

Ademović, N., Tomić, T., Tanić, N., Milić, M., Rakić, M.,& Tanić, N.. (2023). Genomic instability as a prognostic marker in malignant brain cancer. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade, Serbia: Serbian Associaton for Cancer Research., 90-91.
https://hdl.handle.net/21.15107/rcub_ibiss_6234

Ademović N, Tomić T, Tanić N, Milić M, Rakić M, Tanić N. Genomic instability as a prognostic marker in malignant brain cancer. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:90-91.
https://hdl.handle.net/21.15107/rcub_ibiss_6234 .

Ademović, Nejla, Tomić, Tijana, Tanić, Nasta, Milić, Marina, Rakić, Miodrag, Tanić, Nikola, "Genomic instability as a prognostic marker in malignant brain cancer" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):90-91,
https://hdl.handle.net/21.15107/rcub_ibiss_6234 .

TY  - CONF
AU  - Tanić, Nikola
AU  - Dramićanin, Tatjana
AU  - Milovanović, Zorka
AU  - Nedeljković, Milica
AU  - Tomić, Tijana
AU  - Ademović, Nejla
AU  - Murganić, Blagoje
AU  - Tanic, Nasta
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5773
AB  - Breast cancer (BC) is the most frequent type of malignancy and the leading cause
of cancer related death among women worldwide. More than 70% of all diagnosed invasive
BCs express steroid receptors and, as such, are subjected to endocrine therapy.
BC is exceptionally heterogeneous disease and therefore distinct treatment modalities
are necessary to address these differences. The aim of our study was to investigate
the impact of TP53 and PTEN tumor suppressor genes (TSGs) inactivation on BC
response to different treatment modalities, as well as, their possible cooperation, on
post-operative BC samples. To that end the patients were classified, based on applied
adjuvant therapy, into four distinct groups: those that received hormonal therapy
(HT) only, hormonal therapy combined with chemotherapy (HT/CHT), hormonal
therapy combined with chemo and biological therapy (HT/CHT/H), and other systemic
therapies that exclude HT (for example CHT or H). Functional inactivation of
TP53 and PTEN TSG’s were studied by mutation, loss of heterozygosity (LOH) and
hypermethylatyon analysis. Our results revealed that TP53 gene was altered in 63 out
of 90 specimens (70%), while the frequency of PTEN alterations was slightly lower,
54 out of 90 (60%) patients had inactivated PTEN. Simultaneous inactivation was
detected in 43 tested samples (48%) with significant association between two analyzed
TSGs. Further, we found that TP53 status has significant influence on patients’
therapy response. Patients with wild type TP53 show significantly better therapy response
regardless of the type of therapy, compared to carriers of altered p53 gene. In
support of this we showed that hormonally treated women with intact (wt) TP53 gene
had significantly longer survival rate (p=0.000001) when compared to: (i) hormonally
treated women with aberrant TP53gene, (ii) women with intact (wt) p53 subjected to
any of remaining three therapy combinations, and (iii) women with altered TP53 that
belong to second (HT/CHT), third (HT/CHT/H) or forth (systemic Th that exclude
HT) therapy group. Contrary to this, no significance was found between mutational status of PTEN and various treatment modalities. However, significant association
was found between the type of applied therapy and simultaneous alterations of these
two TSGs (p=0.00001).
AB  - Рак дојке је најчешћи тип малигнитета и водећи узрок смрти од канцера код
жена широм света. Више од 70% свих дијагностикованих инвазивних карцинома
дојке експримира стероидне рецепторе и као такви су подобни за ендокрину терапију. Канцер дојке је изузетно хетерогена болест и стога су неопходни различити модалитети лечења да би се превазишле ове разлике. Циљ нашег истраживања
био је да се испита утицај инактивације ТП53 и ПТЕН тумор супресорских гена
(ТСГ) у одговору на различите модалитете лечења на постоперативним узорцима
карцинома дојке. Са тим циљем пацијенткиње су класификоване, на основу примењене ађувантне терапије, у четири различите групе: оне које су примале само
хормонску терапију (ХТ), хормонску терапију у комбинацији са хемиотерапијом
(ХТ/ЦХТ), хормонску терапију у комбинацији са хемиотерапијом и биолошком
терапијом (ХТ). /ЦХТ/Х) и друге системске терапије које искључују ХТ (на пример ЦХТ или Х). Функционална инактивација ТП53 и ПТЕН тумор супресора
је студирана анализом мутационог статуса, губитка хетерозиготности (ЛОХ) и
анализом метилационог статуса. Наши резултати су показали да је ТП53 ген измењен код 63 од 90 узорака (70%), док је учесталост промена ПТЕН гена била
нешто нижа, 54 од 90 (60%) пацијената је имало инактивиран ПТЕН. Симултана
инактивација је детектована у 43 тестирана узорка (48%) са значајном повезаношћу инактивације два анализирана тумор супресор гена.
Даље, показали смо да статус ТП53 има значајан утицај на одговор пацијената
на терапију. Пацијенти са дивљим типом (wt) ТП53 показују значајно бољи терапијски одговор без обзира на врсту терапије, у поређењу са носиоцима измењеног TП53. У прилог овоме показали смо да су хормонски лечене жене са интактним (wt) ТП53 геном имале значајно већу стопу преживљавања (п=0,000001) у
поређењу са: (1) женама леченим хормонсом теерапијом са аберантним ТП53 геном, (2) женама са интактним (wt) TП53 подвргнутим било којој од преостале три терапијске комбинације, и (3) женама са измењеним ТП53 које припадају другој
(ХТ/ЦХТ), трећој (ХТ/ЦХТ/Х) или четвртој (системска терапија која искључује ХТ) терапијској групи. Супротно овоме, нисмо утврдили значајну асоцијацију
између мутационог статуса ПТЕН-а и различитих модалитета лечења. Међутим,
утврђена је значајна повезаност између врсте примењене терапије и истовремених промена ова два тумор супресор гена (п=0,00001).
PB  - Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
T1  - The Role of TP53 and PTEN tumor suppressor genes in response to different breast cancer treatment modalities
T1  - Улога ТП53 и ПТЕН тумор супресор гена у одговору на различите модалитете терапије канцера дојке
SP  - 94
EP  - 97
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5773
ER  - 

@conference{
author = "Tanić, Nikola and Dramićanin, Tatjana and Milovanović, Zorka and Nedeljković, Milica and Tomić, Tijana and Ademović, Nejla and Murganić, Blagoje and Tanic, Nasta",
year = "2022",
abstract = "Breast cancer (BC) is the most frequent type of malignancy and the leading cause
of cancer related death among women worldwide. More than 70% of all diagnosed invasive
BCs express steroid receptors and, as such, are subjected to endocrine therapy.
BC is exceptionally heterogeneous disease and therefore distinct treatment modalities
are necessary to address these differences. The aim of our study was to investigate
the impact of TP53 and PTEN tumor suppressor genes (TSGs) inactivation on BC
response to different treatment modalities, as well as, their possible cooperation, on
post-operative BC samples. To that end the patients were classified, based on applied
adjuvant therapy, into four distinct groups: those that received hormonal therapy
(HT) only, hormonal therapy combined with chemotherapy (HT/CHT), hormonal
therapy combined with chemo and biological therapy (HT/CHT/H), and other systemic
therapies that exclude HT (for example CHT or H). Functional inactivation of
TP53 and PTEN TSG’s were studied by mutation, loss of heterozygosity (LOH) and
hypermethylatyon analysis. Our results revealed that TP53 gene was altered in 63 out
of 90 specimens (70%), while the frequency of PTEN alterations was slightly lower,
54 out of 90 (60%) patients had inactivated PTEN. Simultaneous inactivation was
detected in 43 tested samples (48%) with significant association between two analyzed
TSGs. Further, we found that TP53 status has significant influence on patients’
therapy response. Patients with wild type TP53 show significantly better therapy response
regardless of the type of therapy, compared to carriers of altered p53 gene. In
support of this we showed that hormonally treated women with intact (wt) TP53 gene
had significantly longer survival rate (p=0.000001) when compared to: (i) hormonally
treated women with aberrant TP53gene, (ii) women with intact (wt) p53 subjected to
any of remaining three therapy combinations, and (iii) women with altered TP53 that
belong to second (HT/CHT), third (HT/CHT/H) or forth (systemic Th that exclude
HT) therapy group. Contrary to this, no significance was found between mutational status of PTEN and various treatment modalities. However, significant association
was found between the type of applied therapy and simultaneous alterations of these
two TSGs (p=0.00001)., Рак дојке је најчешћи тип малигнитета и водећи узрок смрти од канцера код
жена широм света. Више од 70% свих дијагностикованих инвазивних карцинома
дојке експримира стероидне рецепторе и као такви су подобни за ендокрину терапију. Канцер дојке је изузетно хетерогена болест и стога су неопходни различити модалитети лечења да би се превазишле ове разлике. Циљ нашег истраживања
био је да се испита утицај инактивације ТП53 и ПТЕН тумор супресорских гена
(ТСГ) у одговору на различите модалитете лечења на постоперативним узорцима
карцинома дојке. Са тим циљем пацијенткиње су класификоване, на основу примењене ађувантне терапије, у четири различите групе: оне које су примале само
хормонску терапију (ХТ), хормонску терапију у комбинацији са хемиотерапијом
(ХТ/ЦХТ), хормонску терапију у комбинацији са хемиотерапијом и биолошком
терапијом (ХТ). /ЦХТ/Х) и друге системске терапије које искључују ХТ (на пример ЦХТ или Х). Функционална инактивација ТП53 и ПТЕН тумор супресора
је студирана анализом мутационог статуса, губитка хетерозиготности (ЛОХ) и
анализом метилационог статуса. Наши резултати су показали да је ТП53 ген измењен код 63 од 90 узорака (70%), док је учесталост промена ПТЕН гена била
нешто нижа, 54 од 90 (60%) пацијената је имало инактивиран ПТЕН. Симултана
инактивација је детектована у 43 тестирана узорка (48%) са значајном повезаношћу инактивације два анализирана тумор супресор гена.
Даље, показали смо да статус ТП53 има значајан утицај на одговор пацијената
на терапију. Пацијенти са дивљим типом (wt) ТП53 показују значајно бољи терапијски одговор без обзира на врсту терапије, у поређењу са носиоцима измењеног TП53. У прилог овоме показали смо да су хормонски лечене жене са интактним (wt) ТП53 геном имале значајно већу стопу преживљавања (п=0,000001) у
поређењу са: (1) женама леченим хормонсом теерапијом са аберантним ТП53 геном, (2) женама са интактним (wt) TП53 подвргнутим било којој од преостале три терапијске комбинације, и (3) женама са измењеним ТП53 које припадају другој
(ХТ/ЦХТ), трећој (ХТ/ЦХТ/Х) или четвртој (системска терапија која искључује ХТ) терапијској групи. Супротно овоме, нисмо утврдили значајну асоцијацију
између мутационог статуса ПТЕН-а и различитих модалитета лечења. Међутим,
утврђена је значајна повезаност између врсте примењене терапије и истовремених промена ова два тумор супресор гена (п=0,00001).",
publisher = "Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina",
title = "The Role of TP53 and PTEN tumor suppressor genes in response to different breast cancer treatment modalities, Улога ТП53 и ПТЕН тумор супресор гена у одговору на различите модалитете терапије канцера дојке",
pages = "94-97",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5773"
}

Tanić, N., Dramićanin, T., Milovanović, Z., Nedeljković, M., Tomić, T., Ademović, N., Murganić, B.,& Tanic, N.. (2022). The Role of TP53 and PTEN tumor suppressor genes in response to different breast cancer treatment modalities. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 94-97.
https://hdl.handle.net/21.15107/rcub_ibiss_5773

Tanić N, Dramićanin T, Milovanović Z, Nedeljković M, Tomić T, Ademović N, Murganić B, Tanic N. The Role of TP53 and PTEN tumor suppressor genes in response to different breast cancer treatment modalities. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina. 2022;:94-97.
https://hdl.handle.net/21.15107/rcub_ibiss_5773 .

Tanić, Nikola, Dramićanin, Tatjana, Milovanović, Zorka, Nedeljković, Milica, Tomić, Tijana, Ademović, Nejla, Murganić, Blagoje, Tanic, Nasta, "The Role of TP53 and PTEN tumor suppressor genes in response to different breast cancer treatment modalities" in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina (2022):94-97,
https://hdl.handle.net/21.15107/rcub_ibiss_5773 .

TY  - CONF
AU  - Nedeljković, Milica
AU  - Stojišić, Jelena
AU  - Tanić, Nasta
AU  - Murganić, Blagoje
AU  - Tomić, Tijana
AU  - Ademović, Nejla
AU  - Tanić, Nikola
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5771
AB  - Lung cancer is the most frequently diagnosed and lethal malignancy in the
world. Lung adenocarcinoma (LAC) and lung squamous cell carcinoma (LSCC)
are two subtypes of non-small cell lung cancer (NSCLC) which differ markedly in
key clinical and biological features. Despite this, they are usually treated similarly.
It is imperative to elucidate the mechanisms behind these differences in order to
implement better therapeutic modalities and biomarkers. Increased expression of
carbonic anhydrases Ca9 and Ca12 was observed in a broad array of tumors. Ca9
and Ca12 have a crucial role in the maintenance of the neutral intracellular pH and
the acidic extracellular microenvironment which stimulates the proliferation and
metastasis of tumor cells. Our aim was to detect possible difference in expression
level of Ca9 and Ca12 in LAC and LSCC, and to investigate whether the expression
of Ca9 and Ca12 was associated with the clinical course and outcome. We evaluated
the Ca9 and Ca12 expressions in 71 lung cancers, 35 (49%) LAC and 36 (51%)
LSCC. After RNA isolation and reverse transcription, relative RNA expression level
was evaluated using Real Time PCR and TaqMan technology. Ca9 and Ca12 expression
status was calculated according to the 2-ΔΔCT method. We used median value
of expression to designate low and high expression groups. High level of Ca9 and
Ca12 expression were detected in 49% (35/71) and 48% (34/71) of NSCLC samples,
respectively. Low levels of expression were identified in the rest of the specimens.
High expression of Ca12 was associated with LSCC subtype (p<0.0001). No associations
between Ca9 or Ca12 expression and clinicopathological parameters were
detected when assessed independently. However, patients with high expression of
both Ca9 and Ca12 lived significantly shorter compared to the Ca9/Ca12 low expression
group, (p=0.02). Our results suggest that Ca12 expression contributes to
the differences observed between LAC and LSCC tumors. The upregulation of Ca12 may promote the aggressive behavior of NSCLC. Ca9-high/Ca12-high expression
constitutes a ‘high risk’ profile in NSCLC.
AB  - Карцином плућа је најчешће дијагностикована и најсмртоноснија малигна болест у свету. Аденокрацином плућа (енг. lung adenocarcinoma, LAC) и карцином сквамозних ћелија плућа (енг. lung squamous cell carcinoma, LSCC) су два подтипа неситноћелијског карцинома плућа са израженим разликама у кључним клиничким и биолошким карактеристикама. Упркос томе, ови подтипови се најчешће лече на врло сличан начин. Изузетно је важно да се разјасне механизми у основи ових разлика како би се успоставили бољи биомаркери и приступи у лечењу. У бројним типовима тумора примећена је повећана експресија карбонске анхидразе (Са) 9 и 12. Са9 и Са12 имају круцијалну улогу у одржавању неутралне унутарћелијске вредности рН и киселе ванћелијске микросредине што стимулише пролиферцију и метастазирање ћелија тумора. Наши циљеви су били да детектујемо могуће разлике у нивоу експресије Са9 и Са12 у LAC и LSCC, и да истражимо да ли је експресија Са9 и Са12 асоцирана са клиничким током и исходом болести. Испитали смо експресију Са9 и Са12 у 71 узорку карцинома плућа, 35 (49%) LAC и 36 (51%) LSCC. Након изолације РНК и реверзне транскрипције, релативни ниво експресије РНК утврђен је коришћењем квантитативног РСR-а у реалном времену базираног на TaqMan технологији. За израчунавање статуса експресије Са9 и Са12 коришћена је 2-ΔΔCT метода. Употребили смо медијану вредности експресије да дефинишемо групе са високом, односно ниском експресијом. Висок ниво експресије Са9 детектован је у 49% (35/71), а Са12 у 48% (34/71) узорака. Низак ниво експресије је идентификован у преосталим узорцима. Висока експресија Са12 била је асоцирана са LSCC подтипом (р<0.0001). Када су експресија Са9 и Са12 посматране независно, није уочена њихова асоцијација са клиничко-хистопатолошким параметрима. Међутим, пацијенти који су истовремено имали високу експресију и Са9 и Са12 су живели значајно краће у односу на пацијенте са ниском експресијом Са9/Са12, (р=0.02). Наши резултати сугеришу да експресија Са12 доприноси разликама уоченим између LAC и LSCC тумора. Појачана експресија Са12 можда подстиче агресивно понашање неситноћелијског карцинома плућа. Са9 висока/Са12 висока експресија представља профил “високог ризика” у неситноћелијском карциному плућа.
PB  - Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
T1  - Differences in carbonic anhydrase 9 and 12 expression in lung adenocarcinoma and lung squamous cell carcinoma
T1  - Разлике у експресији карбонске анхидразе 9 и 12 у аденокарциному плућа и карциному сквамозних ћелија плућа
SP  - 78
EP  - 81
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5771
ER  - 

@conference{
author = "Nedeljković, Milica and Stojišić, Jelena and Tanić, Nasta and Murganić, Blagoje and Tomić, Tijana and Ademović, Nejla and Tanić, Nikola",
year = "2022",
abstract = "Lung cancer is the most frequently diagnosed and lethal malignancy in the
world. Lung adenocarcinoma (LAC) and lung squamous cell carcinoma (LSCC)
are two subtypes of non-small cell lung cancer (NSCLC) which differ markedly in
key clinical and biological features. Despite this, they are usually treated similarly.
It is imperative to elucidate the mechanisms behind these differences in order to
implement better therapeutic modalities and biomarkers. Increased expression of
carbonic anhydrases Ca9 and Ca12 was observed in a broad array of tumors. Ca9
and Ca12 have a crucial role in the maintenance of the neutral intracellular pH and
the acidic extracellular microenvironment which stimulates the proliferation and
metastasis of tumor cells. Our aim was to detect possible difference in expression
level of Ca9 and Ca12 in LAC and LSCC, and to investigate whether the expression
of Ca9 and Ca12 was associated with the clinical course and outcome. We evaluated
the Ca9 and Ca12 expressions in 71 lung cancers, 35 (49%) LAC and 36 (51%)
LSCC. After RNA isolation and reverse transcription, relative RNA expression level
was evaluated using Real Time PCR and TaqMan technology. Ca9 and Ca12 expression
status was calculated according to the 2-ΔΔCT method. We used median value
of expression to designate low and high expression groups. High level of Ca9 and
Ca12 expression were detected in 49% (35/71) and 48% (34/71) of NSCLC samples,
respectively. Low levels of expression were identified in the rest of the specimens.
High expression of Ca12 was associated with LSCC subtype (p<0.0001). No associations
between Ca9 or Ca12 expression and clinicopathological parameters were
detected when assessed independently. However, patients with high expression of
both Ca9 and Ca12 lived significantly shorter compared to the Ca9/Ca12 low expression
group, (p=0.02). Our results suggest that Ca12 expression contributes to
the differences observed between LAC and LSCC tumors. The upregulation of Ca12 may promote the aggressive behavior of NSCLC. Ca9-high/Ca12-high expression
constitutes a ‘high risk’ profile in NSCLC., Карцином плућа је најчешће дијагностикована и најсмртоноснија малигна болест у свету. Аденокрацином плућа (енг. lung adenocarcinoma, LAC) и карцином сквамозних ћелија плућа (енг. lung squamous cell carcinoma, LSCC) су два подтипа неситноћелијског карцинома плућа са израженим разликама у кључним клиничким и биолошким карактеристикама. Упркос томе, ови подтипови се најчешће лече на врло сличан начин. Изузетно је важно да се разјасне механизми у основи ових разлика како би се успоставили бољи биомаркери и приступи у лечењу. У бројним типовима тумора примећена је повећана експресија карбонске анхидразе (Са) 9 и 12. Са9 и Са12 имају круцијалну улогу у одржавању неутралне унутарћелијске вредности рН и киселе ванћелијске микросредине што стимулише пролиферцију и метастазирање ћелија тумора. Наши циљеви су били да детектујемо могуће разлике у нивоу експресије Са9 и Са12 у LAC и LSCC, и да истражимо да ли је експресија Са9 и Са12 асоцирана са клиничким током и исходом болести. Испитали смо експресију Са9 и Са12 у 71 узорку карцинома плућа, 35 (49%) LAC и 36 (51%) LSCC. Након изолације РНК и реверзне транскрипције, релативни ниво експресије РНК утврђен је коришћењем квантитативног РСR-а у реалном времену базираног на TaqMan технологији. За израчунавање статуса експресије Са9 и Са12 коришћена је 2-ΔΔCT метода. Употребили смо медијану вредности експресије да дефинишемо групе са високом, односно ниском експресијом. Висок ниво експресије Са9 детектован је у 49% (35/71), а Са12 у 48% (34/71) узорака. Низак ниво експресије је идентификован у преосталим узорцима. Висока експресија Са12 била је асоцирана са LSCC подтипом (р<0.0001). Када су експресија Са9 и Са12 посматране независно, није уочена њихова асоцијација са клиничко-хистопатолошким параметрима. Међутим, пацијенти који су истовремено имали високу експресију и Са9 и Са12 су живели значајно краће у односу на пацијенте са ниском експресијом Са9/Са12, (р=0.02). Наши резултати сугеришу да експресија Са12 доприноси разликама уоченим између LAC и LSCC тумора. Појачана експресија Са12 можда подстиче агресивно понашање неситноћелијског карцинома плућа. Са9 висока/Са12 висока експресија представља профил “високог ризика” у неситноћелијском карциному плућа.",
publisher = "Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina",
title = "Differences in carbonic anhydrase 9 and 12 expression in lung adenocarcinoma and lung squamous cell carcinoma, Разлике у експресији карбонске анхидразе 9 и 12 у аденокарциному плућа и карциному сквамозних ћелија плућа",
pages = "78-81",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5771"
}

Nedeljković, M., Stojišić, J., Tanić, N., Murganić, B., Tomić, T., Ademović, N.,& Tanić, N.. (2022). Differences in carbonic anhydrase 9 and 12 expression in lung adenocarcinoma and lung squamous cell carcinoma. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 78-81.
https://hdl.handle.net/21.15107/rcub_ibiss_5771

Nedeljković M, Stojišić J, Tanić N, Murganić B, Tomić T, Ademović N, Tanić N. Differences in carbonic anhydrase 9 and 12 expression in lung adenocarcinoma and lung squamous cell carcinoma. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina. 2022;:78-81.
https://hdl.handle.net/21.15107/rcub_ibiss_5771 .

Nedeljković, Milica, Stojišić, Jelena, Tanić, Nasta, Murganić, Blagoje, Tomić, Tijana, Ademović, Nejla, Tanić, Nikola, "Differences in carbonic anhydrase 9 and 12 expression in lung adenocarcinoma and lung squamous cell carcinoma" in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina (2022):78-81,
https://hdl.handle.net/21.15107/rcub_ibiss_5771 .

TY  - JOUR
AU  - Tanić, Nikola
AU  - Dramićanin, Tatjana
AU  - Ademović, Nejla
AU  - Tomić, Tijana
AU  - Murganić, Blagoje
AU  - Milovanović, Zorka
AU  - Nedeljković, Milica
AU  - Tanić, Nasta
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5362
AB  - Introduction. Breast cancer (BC) is the most frequent type of malignancy and the leading cause of cancer related death among women worldwide. BC is exceptionally heterogeneous disease and therefore distinct treatment modalities are necessary to address these differences. The aim of our study was to investigate the impact of TP53 and PTEN tumor suppressor genes (TSGs) inactivation on BC response to different treatment modalities and their possible cooperation, on post-operative BC samples.
Methods. Patients were classified, based on applied adjuvant therapy, into four distinct groups: those that received hormonal therapy (HT) only, hormonal therapy combined with chemotherapy (HT/CHT), hormonal therapy combined with chemo and biological therapy (HT/CHT/H), and other systemic therapies that exclude HT. Functional inactivation of TP53 and PTEN TSG’s were studied by mutation, loss of heterozygosity (LOH) and hypermethylation analysis.
Results. Our results revealed that TP53 gene was altered in 63 out of 90 specimens (70%), while the frequency of PTEN alterations was slightly lower, 54 out of 90 (60%). Simultaneous inactivation was detected in 43 tested samples (48%) with significant association between two analyzed TSGs. Further, we found that TP53 status has significant influence on patients’ therapy response. Contrary to this, no significance was found between mutational status of PTEN and various treatment modalities. However, significant association was found between the type of applied therapy and simultaneous alterations of these two TSGs (p = 0.00001). 
Conclusion. Patients with wtTP53 show significantly better therapy response regardless of the type of therapy, compared to carriers of altered TPp53 gene.
AB  - Uvod. Rak dojke (RD) je najčešći tip maligniteta i vodeći uzrok smrti od raka kod žena širom sveta. RD
je izuzetno heterogena bolest i stoga su neophodni različiti modaliteti lečenja da bi se pokrile ove
razlike. Cilj našeg istraživanja je bio da se ispita uticaj inaktivacije TP53 i PTEN tumor supresorskih
gena (TSG) na odgovor RD na različite modalitete lečenja, kao i njihova moguća saradnja u tome, na
postoperativnim uzorcima RD.
Metode. Pacijentkinje su klasifikovane, na osnovu primenjene adjuvantne terapije, u četiri različite
grupe: one koje su primale samo hormonsku terapiju (HT), hormonsku terapiju u kombinaciji sa hemoterapijom (HT/CHT), hormonsku terapiju u kombinaciji sa hemoterapijom i biološkom terapijom
(HT/CHT/H) i druge sistemske terapije koje isključuju HT. Funkcionalna inaktivacija TP53 i PTEN TSG
je proučavana analizom mutacionog statusa, gubitka heterozigotnosti (LOH) i metilacionog statusa.
Rezultati. Naši rezultati su pokazali da je TP53 gen izmenjen kod 63 od 90 pacijenata (70%), dok je
učestalost promena PTEN gena bila nešto niža, 54 od 90 (60%). Simultana inaktivacija je detektovana
u 43 testirana uzorka (48%) sa značajnom povezanošću između dva analizirana TSG-a. Dalje, pokazali
smo da status TP53 ima značajan uticaj na odgovor pacijenata na terapiju. Suprotno ovome, nismo
pokazali značajnu asocijaciju između mutacionog statusa PTEN-a i različitih modaliteta lečenja. Međutim, utvrđena je značajna povezanost između primenjenih terapija i simultanih inaktivacija ova
dva TSG-a (p = 0,00001).
Zaključak. Pacijenti sa wtTP53 pokazuju značajno bolji terapijski odgovor bez obzira na vrstu terapije u poređenju sa nosiocima mutiranog TP53 gena.
PB  - Republika Srpska, Bosna i Hercegovina: Univerzitet u Istočnom Sarajevu - Medicinski fakultet Foča
T2  - Biomedicinska istraživanja
T1  - The impact of TP53 and PTEN tumor suppressor genes on response to different breast cancer treatment modalities
T1  - Uticaj tumor supresorskih gena TP53 i PTEN na odgovor na različite načine lečenja raka dojke
IS  - 2
VL  - 13
DO  - 10.5937/BII2202105T
ER  - 

@article{
author = "Tanić, Nikola and Dramićanin, Tatjana and Ademović, Nejla and Tomić, Tijana and Murganić, Blagoje and Milovanović, Zorka and Nedeljković, Milica and Tanić, Nasta",
year = "2022",
abstract = "Introduction. Breast cancer (BC) is the most frequent type of malignancy and the leading cause of cancer related death among women worldwide. BC is exceptionally heterogeneous disease and therefore distinct treatment modalities are necessary to address these differences. The aim of our study was to investigate the impact of TP53 and PTEN tumor suppressor genes (TSGs) inactivation on BC response to different treatment modalities and their possible cooperation, on post-operative BC samples.
Methods. Patients were classified, based on applied adjuvant therapy, into four distinct groups: those that received hormonal therapy (HT) only, hormonal therapy combined with chemotherapy (HT/CHT), hormonal therapy combined with chemo and biological therapy (HT/CHT/H), and other systemic therapies that exclude HT. Functional inactivation of TP53 and PTEN TSG’s were studied by mutation, loss of heterozygosity (LOH) and hypermethylation analysis.
Results. Our results revealed that TP53 gene was altered in 63 out of 90 specimens (70%), while the frequency of PTEN alterations was slightly lower, 54 out of 90 (60%). Simultaneous inactivation was detected in 43 tested samples (48%) with significant association between two analyzed TSGs. Further, we found that TP53 status has significant influence on patients’ therapy response. Contrary to this, no significance was found between mutational status of PTEN and various treatment modalities. However, significant association was found between the type of applied therapy and simultaneous alterations of these two TSGs (p = 0.00001). 
Conclusion. Patients with wtTP53 show significantly better therapy response regardless of the type of therapy, compared to carriers of altered TPp53 gene., Uvod. Rak dojke (RD) je najčešći tip maligniteta i vodeći uzrok smrti od raka kod žena širom sveta. RD
je izuzetno heterogena bolest i stoga su neophodni različiti modaliteti lečenja da bi se pokrile ove
razlike. Cilj našeg istraživanja je bio da se ispita uticaj inaktivacije TP53 i PTEN tumor supresorskih
gena (TSG) na odgovor RD na različite modalitete lečenja, kao i njihova moguća saradnja u tome, na
postoperativnim uzorcima RD.
Metode. Pacijentkinje su klasifikovane, na osnovu primenjene adjuvantne terapije, u četiri različite
grupe: one koje su primale samo hormonsku terapiju (HT), hormonsku terapiju u kombinaciji sa hemoterapijom (HT/CHT), hormonsku terapiju u kombinaciji sa hemoterapijom i biološkom terapijom
(HT/CHT/H) i druge sistemske terapije koje isključuju HT. Funkcionalna inaktivacija TP53 i PTEN TSG
je proučavana analizom mutacionog statusa, gubitka heterozigotnosti (LOH) i metilacionog statusa.
Rezultati. Naši rezultati su pokazali da je TP53 gen izmenjen kod 63 od 90 pacijenata (70%), dok je
učestalost promena PTEN gena bila nešto niža, 54 od 90 (60%). Simultana inaktivacija je detektovana
u 43 testirana uzorka (48%) sa značajnom povezanošću između dva analizirana TSG-a. Dalje, pokazali
smo da status TP53 ima značajan uticaj na odgovor pacijenata na terapiju. Suprotno ovome, nismo
pokazali značajnu asocijaciju između mutacionog statusa PTEN-a i različitih modaliteta lečenja. Međutim, utvrđena je značajna povezanost između primenjenih terapija i simultanih inaktivacija ova
dva TSG-a (p = 0,00001).
Zaključak. Pacijenti sa wtTP53 pokazuju značajno bolji terapijski odgovor bez obzira na vrstu terapije u poređenju sa nosiocima mutiranog TP53 gena.",
publisher = "Republika Srpska, Bosna i Hercegovina: Univerzitet u Istočnom Sarajevu - Medicinski fakultet Foča",
journal = "Biomedicinska istraživanja",
title = "The impact of TP53 and PTEN tumor suppressor genes on response to different breast cancer treatment modalities, Uticaj tumor supresorskih gena TP53 i PTEN na odgovor na različite načine lečenja raka dojke",
number = "2",
volume = "13",
doi = "10.5937/BII2202105T"
}

Tanić, N., Dramićanin, T., Ademović, N., Tomić, T., Murganić, B., Milovanović, Z., Nedeljković, M.,& Tanić, N.. (2022). The impact of TP53 and PTEN tumor suppressor genes on response to different breast cancer treatment modalities. in Biomedicinska istraživanja
Republika Srpska, Bosna i Hercegovina: Univerzitet u Istočnom Sarajevu - Medicinski fakultet Foča., 13(2).
https://doi.org/10.5937/BII2202105T

Tanić N, Dramićanin T, Ademović N, Tomić T, Murganić B, Milovanović Z, Nedeljković M, Tanić N. The impact of TP53 and PTEN tumor suppressor genes on response to different breast cancer treatment modalities. in Biomedicinska istraživanja. 2022;13(2).
doi:10.5937/BII2202105T .

Tanić, Nikola, Dramićanin, Tatjana, Ademović, Nejla, Tomić, Tijana, Murganić, Blagoje, Milovanović, Zorka, Nedeljković, Milica, Tanić, Nasta, "The impact of TP53 and PTEN tumor suppressor genes on response to different breast cancer treatment modalities" in Biomedicinska istraživanja, 13, no. 2 (2022),
https://doi.org/10.5937/BII2202105T . .

TY  - CONF
AU  - Nedeljković, Milica
AU  - Dramićanin, Tatjana
AU  - Prvanović, Mirjana
AU  - Murganić, Blagoje
AU  - Tomić, Tijana
AU  - Ademović, Nejla
AU  - Milovanović, Zorka
AU  - Tanić, Nikola
AU  - Tanić, Nasta
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6692
AB  - Background: Breast cancer (BC) is the most frequent type of malignancy and the leading cause of cancer related death among women worldwide. Multiple interconnected factors determine BC response to therapy and clinical outcome. TP53 and PTEN are the most frequently altered tumor suppressor genes (TSGs) in human cancers. Material and methods: To determine the potential influence of TSGs on the response to therapy we analyzed alterations of TP53 and PTEN in 90 BC specimens. The specimens were stratified based on systemic adjuvant therapy (hormonal therapy only (HT), HT and chemotherapy (HT/CHT), HT/CHT and biological therapy (HT/CHT/H). Functional inactivation of TP53 by mutations and/or loss of heterozygosity (LOH) and PTEN by LOH and/or promoter hypermethylation, were tested using single-strand conformational polymorphism (SSCP) analysis, gene sequencing, fragment analysis and methylation-specific PCR (MS-PCR) methods respectively. Results: Altered TP53 was found in 63/90 specimens (70%) while 54/90 (60%) had inactivated PTEN. Inactivation of PTEN was more frequent in tumors with altered TP53. Patients with altered TP53, lived shorter (p=0.0007) compared to those with wild type (wt) gene. The survival of patients with both TSGs altered was shorter compared to wt genes (p=0.024). Patients with wtTP53 treated with HT had longer survival (p=0.000001) when compared to all other groups. Women with both TSGs altered who received tamoxifen lived shorter than those on HT with both/one TSGs intact (p = 0.03). Conclusion: Patients with wtTP53 showed significantly better therapy response regardless of type of therapy, compared to carriers of altered TP53.
PB  - Beograd : Srpsko društvo istraživača raka
C3  - Abstract book: 5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5: Translational Potential of Cancer Research in Serbia; 2021 Dec 3; Virtual event
T1  - Role of TP53 and PTEN tumor suppressor genes alterations in breast cancer response to therapy
SP  - 38
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6692
ER  - 

@conference{
author = "Nedeljković, Milica and Dramićanin, Tatjana and Prvanović, Mirjana and Murganić, Blagoje and Tomić, Tijana and Ademović, Nejla and Milovanović, Zorka and Tanić, Nikola and Tanić, Nasta",
year = "2021",
abstract = "Background: Breast cancer (BC) is the most frequent type of malignancy and the leading cause of cancer related death among women worldwide. Multiple interconnected factors determine BC response to therapy and clinical outcome. TP53 and PTEN are the most frequently altered tumor suppressor genes (TSGs) in human cancers. Material and methods: To determine the potential influence of TSGs on the response to therapy we analyzed alterations of TP53 and PTEN in 90 BC specimens. The specimens were stratified based on systemic adjuvant therapy (hormonal therapy only (HT), HT and chemotherapy (HT/CHT), HT/CHT and biological therapy (HT/CHT/H). Functional inactivation of TP53 by mutations and/or loss of heterozygosity (LOH) and PTEN by LOH and/or promoter hypermethylation, were tested using single-strand conformational polymorphism (SSCP) analysis, gene sequencing, fragment analysis and methylation-specific PCR (MS-PCR) methods respectively. Results: Altered TP53 was found in 63/90 specimens (70%) while 54/90 (60%) had inactivated PTEN. Inactivation of PTEN was more frequent in tumors with altered TP53. Patients with altered TP53, lived shorter (p=0.0007) compared to those with wild type (wt) gene. The survival of patients with both TSGs altered was shorter compared to wt genes (p=0.024). Patients with wtTP53 treated with HT had longer survival (p=0.000001) when compared to all other groups. Women with both TSGs altered who received tamoxifen lived shorter than those on HT with both/one TSGs intact (p = 0.03). Conclusion: Patients with wtTP53 showed significantly better therapy response regardless of type of therapy, compared to carriers of altered TP53.",
publisher = "Beograd : Srpsko društvo istraživača raka",
journal = "Abstract book: 5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5: Translational Potential of Cancer Research in Serbia; 2021 Dec 3; Virtual event",
title = "Role of TP53 and PTEN tumor suppressor genes alterations in breast cancer response to therapy",
pages = "38",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6692"
}

Nedeljković, M., Dramićanin, T., Prvanović, M., Murganić, B., Tomić, T., Ademović, N., Milovanović, Z., Tanić, N.,& Tanić, N.. (2021). Role of TP53 and PTEN tumor suppressor genes alterations in breast cancer response to therapy. in Abstract book: 5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5: Translational Potential of Cancer Research in Serbia; 2021 Dec 3; Virtual event
Beograd : Srpsko društvo istraživača raka., 38.
https://hdl.handle.net/21.15107/rcub_ibiss_6692

Nedeljković M, Dramićanin T, Prvanović M, Murganić B, Tomić T, Ademović N, Milovanović Z, Tanić N, Tanić N. Role of TP53 and PTEN tumor suppressor genes alterations in breast cancer response to therapy. in Abstract book: 5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5: Translational Potential of Cancer Research in Serbia; 2021 Dec 3; Virtual event. 2021;:38.
https://hdl.handle.net/21.15107/rcub_ibiss_6692 .

Nedeljković, Milica, Dramićanin, Tatjana, Prvanović, Mirjana, Murganić, Blagoje, Tomić, Tijana, Ademović, Nejla, Milovanović, Zorka, Tanić, Nikola, Tanić, Nasta, "Role of TP53 and PTEN tumor suppressor genes alterations in breast cancer response to therapy" in Abstract book: 5th Congress of the Serbian Association for Cancer Research with International Participation SDIR-5: Translational Potential of Cancer Research in Serbia; 2021 Dec 3; Virtual event (2021):38,
https://hdl.handle.net/21.15107/rcub_ibiss_6692 .