Immunohistochemical Expression of “c-MET” in Breast Carcinomas

Abstract

BACKGROUND: Targeted therapies achieved great success in managing breast cancer, however, triple negative breast cancers (TNBCs) lack the expression of traditional therapeutic targets, and other subtypes develop resistance to current therapies. The c-MET receptor emerged as a potential target with well documented pro-proliferative pro-motility downstream signals and wide network of crosstalk with other effectors. Some reports describe a preferential expression of c-MET in TNBCs and promising results in early anti-c-MET clinical trials. However, the main cause of failure of these trials was attributed to patient selection.
 AIM: The objectives of the study were to assessment of c-MET in subtypes of breast cancer and its association with other clinicopathological variables that may predict its expression and possibly establish other rationales to refine patient selection for clinical trials.
 MATERIALS AND METHODS: Retrospective immunohistochemical study assessing c-MET (clone SP44) in 55 cases of breast carcinoma. The expression of c-MET> 5% was considered positive.
 RESULTS: c-MET was detected in 42% of cases. A statistically significant association of c-MET with extremes of age, advanced prognostic stage, carcinoma with medullary features, and high tumor infiltrating lymphocytes (TILs) was observed for the first time in our study. Grade III, hormone receptor negativity and TNBCs were also significantly associated with c-MET. Only negative progesterone receptor (PR) and high TILs were independently associated with c-MET in a multivariate analysis (p < 0.05). No significant association between c-MET and multifocality, size, node status, anatomic stage, lymphovascular or perineural invasion, and Ki-67 expression.
 CONCLUSION: PR negativity and high TILs might be useful c-MET predictors and selection tools for clinical trials but further studies are needed to validate the unprecedented findings which may not only aid in patient selection but may also inspire new paradigms in future studies.