CORRELATION OF CLINICOPATHOLOGICAL FINDINGS AND C5AR2 EXPRESSION IN BREAST CANCER

Abstract

The breast cancer is the most prevalent cancer among females worldwide. According to Shaukat Khanum Memorial Hospital statistics during the year 2022, breast cancer was the leading cancer among the top ten malignancies in adult females accounting for almost 1/2 of the cancer cases alone (51.1%) (Shahid, et al.,2023). The tumor microenvironment plays a central role in tumor proliferation and invasion via cancer-associated fibroblasts, macrophages, and various other mediators like complement, chemokines. Complement component C5a is a potent anaphylatoxin and chemotactic agent. Its receptor C5aR2-mediated inflammatory response is partly responsible for tumorigenesis. The C5aR2 mRNA is detected in human peripheral blood leukocytes, platelets, bone marrow, spleen, and other organs of which neutrophils are the most abundant source of C5aR2 (Ting, Malgorzata, Ke li, 2017). Objectives were to evaluate the expression of C5aR2 (GPR77) expression in stromal and epithelial cells of breast carcinoma and to determine the correlation of C5aR2 (GPR77) expression in breast carcinoma with clinicopathological parameters. It was a cross-sectional study carried out at PNS Shifa Hospital, Karachi, for a period of six months. 128 formalin fixed paraffin-embedded tumor specimens of breast cancer patients were selected and examined for immunohistochemical expression of C5aR2, using Rabbit polyclonal C5aR2 antibodies IgG type, in breast cancer cells and stromal cells. Clinical and pathological records were reviewed for data collection. The results of immunohistochemistry were correlated with clinicopathological parameters of breast cancer. This study was conducted to determine the correlation of complement receptor C5aR2 with clinicopathological parameters of breast cancer (age, receptor status, stage, grade, proliferation marker Ki-67), using a simplified protocol. The results revealed increased C5aR2 expression in tumor cells as compared to stromal cells. An upregulation of C5aR2 expression was observed in old age. The expression of C5aR2 viii increased with the increasing grade and advancing stage. This experiment showed a strong association of C5aR2 with hormone receptors and HER2. In tumor cells, Luminal B showed the highest C5aR2 expression whereas in stromal cells C5aR2 expression was frequently linked with TNBC. Increased C5aR2 expression was identified in tumors with poor treatment response while decreased C5aR2 expression was observed in definite tumor response. High levels of Ki-67 were frequently associated with elevated C5aR2 expression in tumor cells.C5aR2 was also found to be correlated with the infiltration of immune cells, especially macrophages. The current study also revealed overexpression of C5aR2 in the endothelium of blood vessels found in the stroma of breast cancer. In conclusion, our study highlights the significance of C5aR2 expression in tumor and stromal cells of breast cancer, its involvement in chemoresistance, and immune infiltration. Thereby indicating its potential as a valuable prognostic marker and therapeutic target in breast cancer management.