IMMUNOHISTOCHEMICAL EVALUATION OF PD-L1 AND CD 8 +T CELLS IN BREAST CARCINOMAS; ITS RELATION WITH CLINICOPATHOLOGICAL PARAMETERS

Abstract

Breast carcinoma is the most common malignancy in women worldwide. It is also the most common malignancy in adults in Asia and in Pakistan. Many elements are responsible for its progression which include both genetic and hormonal causes. It is a diverse disease which can be classified according to its histological presentation and molecular status. It is now appreciated that tumors comprise of not only neoplastic cells, but several surrounding cells in the stroma, which is called the tumour microenvironment. One of the most important constituents are the CD8+ T cells. The response of CD8+ cells relies on equilibrium between co-stimulatory and co-inhibitory signals. One such co- inhibitory receptor is the programmed cell death receptor (PD-1), expressed by activated lymphocytes. This binds to its ligand PD-L1 to inhibit cytotoxic T cells, thereby limiting their functions and keeping a balance. However, now it has been proven that malignant cells also express the PD-L1 receptor, thereby evading the immune system and aiding in tumour cell proliferation. PD-L1 has been seen to be expressed in a variety of tumours like non -small cell lung cancer, melanomas, ovarian carcinomas and colorectal carcinomas. Over the years, the PD-1/PD-L1 pathway has also attracted a significant amount of attention for its role it plays in the progression of breast cancers. This study was undertaken to evaluate PD-L1 expression and CD8+ T cell count in breast cancer samples and to determine their co relation with various clinicopathological parameters. A cross sectional study was conducted in PNS Shifa Hospital, Karachi during a period of one year. 70 cases of breast cancer were extracted and examined for immunohistochemical expression of PD-L1 and CD8+T cells. The results of immunohistochemistry were correlated with various clinicopathological parameters namely age, histopathological variant, grade, stage, individual hormone receptor status, molecular subtypes, lymph node involvement and lymphovascular invasion. Out of 70 cases, 30 (42.9%) showed high PD-L1 positivity and 55 out of 70 cases (78.6%) showed low CD8+ T cell count. 31.9% of cases had both PD-L1 high positivity and low CD8+ T cell count. A strong significant association was observed between PD-L1 expression and PR negative status. Out of the molecular subtypes, the triple negative category had greatest number of cases with PD-L1 high positivity (50%),thus suggesting that these markers can be taken an indicators for aggressive tumours. This study is one of the first of its kind which has assessed expression of PD-L1 and CD8+ T cells in breast tumours in Karachi, Pakistan. The detection of PD-L1 in breast carcinomas can aid in the selection of proper immunotherapeutic drugs of the treatment of breast cancer patients