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
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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.
