Clinicopathological Study of the Immunohistological Expression of mTOR and Phosphorylated mTOR in Renal Cell Carcinoma

Abstract

Objective: Renal cell carcinoma (RCC) accounts for 3-5% of all cancers, and approximately 15% of these are metastatic at diagnosis. Treatment of metastatic RCC often relies on molecular targeted drug therapy, which has become the mainstream approach. Recently, the mTOR inhibitors are one typical molecular targeting drug for metastatic RCC. The mTOR is a type of serine/threonine kinase from the phosphatidylinositol kinase-related kinase family. Activation of its pathway has been found to enhance cancer cell growth, apoptosis inhibition and angiogenesis. The aim of this study was to determine the relevance of mTOR expression and activation and to analyze their putative role as a biomarker for systemic treatment in RCC.

Materials: We conducted a clinicopathological verification by performing an immunostaining of mTOR and p-mTOR from RCC specimens from 210 patients who underwent nephrectomy or partial nephrectomy at the Jikei University Hospital following RCC diagnosis.

Results: The mTOR and p-mTOR were expressed mainly in the cytoplasm and cell membrane in 21.1% and 35.4% of all RCC specimens, respectively. Our findings showed no statistically significant difference in terms of individual clinical features, such as gender, histological type, tumor diameter, or prognosis. The p-mTOR expression tended to suggest a poor prognosis but did not show a statistically significant difference. As for RCC subtype, 21% of clear cell RCC showed mTOR expression, and papillary RCC had high mTOR expression frequency (71%), whereas chromophobe RCC had relatively low frequency (8%).

Conclusions: As p-mTOR expression tended to suggest a poor prognosis, further analyses of the expression of the mTOR signaling pathway might contribute to a precision medicine for advanced RCC.