PD-L1 expression and CD274 gene alteration in triple-negative breast cancer: implication for prognostic biomarker

PURPOSE: To estimate the therapeutic potential of PD-L1 inhibition in breast cancer, we evaluated the prevalence and significance of PD-L1 protein expression with a validated antibody and CD274 gene alternation in a large cohort of triple negative breast cancer (TNBC) and correlated with clinicopathological data and patients overall survival. METHODS: Immunohistochemistry and in situ mRNA hybridization was used to detect PD-L1 protein and mRNA expression in tumor tissues from 183 TNBC patients respectively. Fluorescence in situ hybridization analysis was performed on PD-L1 strong expression samples to assess copy number on chromosome 9p24.1 of CD274 gene. RESULTS: Expression of PD-L1 by immune cells was observed in 4.9 % of TNBC, while expression by tumor cells accounted for 8.7 %. There was a high concordance in PD-L1 protein expression and PDL1 mRNA expression. Samples with PD-L1 strong expression were found to have a CD274 gene copy number gain. PD-L1 expression was correlated with higher tumor grade, but was independent of menopausal status, lymph nodes metastasis, histological subtype and tumor size. In addition, we used precise stratification of PD-L1 expression on tumor or immune cells of certain breast cancer subtype and suggested that patients with PD-L1 expression in basal-like tumors by immune cells or with CD274 gene copy number gain had a longer disease-specific overall survival. CONCLUSIONS: Our findings may promote the more precise analysis of PD-L1 expression in breast cancer and aid the selection of patients who may benefit from immune therapy.