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)
2023
Authors:
Medić-Milijić, NatašaJovanić, Irena
Nedeljković, Milica
Spurnić, Igor
Milovanović, Zorka
Ademović, Nejla
Tanić, Nikola
Tanić, Nasta
Contributors
Arsenijević, NebojšaDocument Type:
Conference object (Published version)
,
© 2023 by the Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine, Kragujevac, Serbia
Metadata
Show full item recordAbstract:
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.
Keywords:
PD-L1; AR; EGFR; Ki67Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
In:
- Arsenijević N, editor. 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; 2023. p. 67-70.