Alpha – SMA and the Cancer – Stroma Crosstalk: Unveiling the Invisible Player in Breast Carcinogenesis

Abstract Introduction: Breast cancer is a heterogeneous group of diseases that exhibit various clinical characteristics, course of disease, and response to treatment. In carcinomas, neoplastic epithelial cells are found alongside a biologically diverse stroma made up of multiple stromal cell types and extracellular matrix (ECM) components, all contributing to the complexity of the tumor microenvironment. A significant presence of myofibroblasts, identified by their expression of alpha-smooth muscle actin (α-SMA), has been consistently detected in the stroma of most invasive human breast cancers. However, their exact role in tumor progression remains not well understood. Therefore, this study aims to examine the relationship between the desmoplastic reaction and the clinicopathological features of invasive breast cancer using immunohistochemical analysis. Objectives: The study aims; ● To evaluate the expression of alpha smooth muscle actin (α- SMA) in the stromal component of invasive breast carcinoma using immunohistochemistry. ● To correlate α- SMA expression with histopathological features such as lymphovascular invasion, lymph node involvement. Methodology: Retrospective study, study period - 2 years, gross examination, followed by tissue processing and staining with h and e. Representative block of each lesion subjected to IHC marker Alpha SMA and its expression is evaluated. Results ● Total 34 cases were included ● Mean age of presentation was 52.94 ● Gender – 32 females and 2 males ● Majority cases studied were invasive breast carcinoma, followed by invasive lobular carcinoma, 1 case each of mucinous carcinoma and carcino sarcoma. ● Alpha SMA under expression (score 0 and 1) in 17 cases and overexpression (score 2) in 17 cases. ● Alpha SMA overexpression showed statistical significance with lymph node metastasis and lymphovascular invasion Conclusion: This study demonstrates a statistically significant association between alpha SMA expression and adverse prognostic indicators, including lymph node metastasis and lymphovascular invasion, in invasive breast carcinoma. These findings suggest that alpha SMA may serve as a potential marker of tumor aggressiveness and stromal activation, reinforcing its role in the cancer – stroma interplay. Assessing alpha SMA expression could thus offer valuable insights into tumor behaviour and aid in risk stratification of breast carcinoma patients