Immunohistochemical Study on Programmed Death Ligand 1 (PD-L1) in Breast Carcinoma and its Correlation with the Clinicopathological Parameters

Abstract

Abstract Background Breast cancer (BC) is considered to be the second highest cause of cancer-related death in women, accounting for 15% of all female cancer-related deaths globally, despite major advancements in early detection and treatment methods. Traditionally, BC has not been considered as an immunogenic tumour, especially when compared to other solid tumours like lung or melanoma. However, a rapidly expanding body of evidence indicates significant immunogenic variability among various BC subtypes, with hormone receptor-negative BC being typically more immunogenic than hormone receptor-positive cancers. Programmed death ligand-1 (PD-L1) is a transmembrane protein, found in a variety of normal tissue cells and also in a wide range of epithelial malignancies, including breast carcinoma. Binding of PD-L1, expressed on tumor cells, to its receptor PD-1, expressed on activated T cells and B cells, disrupts effector immune functions. Antibodies targeting PD-L1 have been approved for treating a wide range of malignancies including breast cancer especially unresectable and metastatic triple negative breast cancer (TNBC). However, PD-L1 expression and its prognostic role in BC is still the target of several researches in order to maximize its therapeutic role in different clinicopathological settings. Objectives to evaluate immunohistochemical expression of PD-L1 in tumour cells and tumour infiltrating lymphocytes (TILs) in different types of breast carcinoma and to correlate between PD-L 1 expression and clinicopathological variables. Material and Methods Ninety cases of breast carcinoma mastectomy specimens were collected and stained immunohistochemically for PD-L1. PD-L1 expression was evaluated in TCs and TILs in the two setting of cases; (Group A) in which the patients didn’t receive preoperative neoadjuvant chemotherapy (NAC) and (Group B) in which the patients received preoperative NAC. The expression of PD-L1 was correlated with clinicopathological parameters. Survival analysis was conducted to correlate disease-free survival (DFS) with PD-L1 expression. Results In cases of Group A (Those didn’t receive preoperative NAC), (31.1%) of cases showed PD-L1 expression by tumor cells [PD-L1 (TCs)] and (47.5%) showed PD-L1 expression by tumor infiltrating lymphocytes [PD-L1 (TILs)]. PD-L1 (TCs) and PD-L1 (TILs) expression were significantly associated with histologic type of invasive duct carcinoma, NST, grade 2, presence of carcinoma in situ, negative hormone receptors, high proliferation index (Ki-67), molecular subtype of TNBC and high level of TILs. In cases received preoperative NAC (Group B), (13.8%) of cases showed PD-L1 expression by tumor cells and (41.4%) showed PD- L1 expression by tumor infiltrating lymphocytes. PD-L1 (TCs) expression was significantly associated with high level of TILs. While PD-L1 (TILs) expression was significantly associated with presence of carcinoma in situ, negative hormone receptors, high proliferation index (Ki-67) and molecular subtype of TNBC. The correlation between PD-L1 expression in TCs and TILs and DFS was statistically insignificant. Conclusion PD-L1 immunohistochemical expression in breast carcinoma is much more prevalent in TILs than TCs and both PD-L1 (TCs) and PD- L1 (TILs) are significantly associated with high proliferation index (K i-67), non-luminal subtypes (TNBC and HER2 Positive) and high TILs level, suggesting that they may be important candidates for anti-PD- 1/PD-L1 therapy.