Immunohistochemical expression of phospho-mTOR protein in breast carcinoma tissues and correlation with clinicopathologic parameters.

Abstract

e13556 Background: The mammalian target of rapamycin (m-TOR) kinase plays a central role in coordinating cell growth in response to mitogens, amino acid and energy sufficiency. The pathway leading to mTOR activation by these factors, is important for the regulation of protein synthesis and cell survival with implications in carcinogenesis. For these reasons, mTOR is currently under investigation as a potential target for anti-cancer therapy. The aim of this study was to determine the phospho-mTOR (p-mTOR) kinase expression in breast cancer tissues and the relationships with clinicopathological parameters of the breast tumors. Methods: We investigated the status of p-mTOR, in 140 breast carcinomas by immunohistochemistry. Western blot analysis was performed to verify the expression levels of p-mTOR. The relationship of protein expression with clinicopathological data and the correlations of protein expression levels were explored. Multiple logistic regression analyses with stepwise method was used in order to find independent factors associated wth p-mTOR. Results: 47.1% of the patients were p-mTOR positive. In univariate analyses a greater proportion of p-mTOR positive patients was found in those having progesterone receptors, in those hving higher grades of differentiation. When multiple analysis was conducted the only factor that was independently associated with p-mTOR kinase was the tumors grade of differentiation adjusted for age. Subjects with moderate grade of differentiation had greater likelihood for being p-mTOR positive compared to those with low grade of differentiation with odds ratio equal to 3.869 (95% CI: 1.35-11.04, p=0.012). Conclusions: The kinase p-mTOR was found in the neoplastic cells of almost half of the patients were enrolled. Overexpression of p-mTOR was correlated with well-to-moderately differentiated tumors (p<0.001) Our results indicate that dysregulation of the p-mTOR pathway may have an important role in the development of breast carcinoma, but not necessarily in the progression of the disease.