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

Lei Guo,Yun Ling,Yi Fang,Tian Qiu,Hongying Yang,Wenbin Li,Lin Dong,Jianming Ying,Xinxin Zhu

doi:10.1186/s40064-016-2513-x

Abstract

PurposeTo 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.MethodsImmunohistochemistry 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.ResultsExpression 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.ConclusionsOur 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.

Highlights

Immune responses are fine-tune regulated through a combination of stimulatory and inhibitory molecules and signal pathways (Dunn et al 2002)
Expression of programmed death ligand 1 (PD-L1) by immune cells was observed in 4.9 % (9/183) of Triple-negative breast cancers (TNBC), while expression by tumor cells accounted for 8.7 % (16/183)
PD-L1 expression was correlated with higher tumor grade of TNBC, but was independent of menopausal status, lymph nodes metastasis, histological subtype and tumor size

Summary

Introduction

Immune responses are fine-tune regulated through a combination of stimulatory and inhibitory molecules and signal pathways (Dunn et al 2002). Guo et al SpringerPlus (2016) 5:805 tumor cells and tumor-infiltrating immune cells (Taube et al 2012). Triple-negative breast cancers (TNBC) are defined as tumors that lack estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor (HER2) expression. These tumors account for 10–20 % of all breast cancers and are often associated with lymphocytic infiltration, higher grade and are biologically more aggressive (Badve et al 2011). There is still not a unanimous agreement on whether PD-L1 expression in immune cells or tumor cells is an independent negative prognostic factor in breast cancer

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Conclusion