Expression of phospho-mTOR kinase is abundant in colorectal cancer and associated with left-sided tumor localization

PURPOSE: To investigate the significance of mammalian target of rapamycin (mTOR) in colorectal cancers. mTOR has recently been suggested as a prognostic biomarker and therapeutic target in an array of human cancers.

FINDINGS: phospho-mTOR (p-mTOR) expression was analyzed by immunohistochemistry (IHC) on a tissue microarray containing 1800 colorectal cancers (CRC). Clinical follow-up data were available from all cancer patients. Positive p-mTOR immunostaining was seen in 83.5% of 1640 interpretable CRC and was considered weak in 862 (52.5%) and strong in 508 cases (31.0%). Matching clinico-pathological parameters were available in 1580 cases. p-mTOR staining was more frequent in tubular adenocarcinomas than in the less common histological subtypes (mucinous, medullary, signet cell; P=0.0163) and significantly linked to carcinomas of the left-sided colon and rectum as compared to right-sided CRC (P=0.0066). There was no significant association between p-mTOR expression and patients' gender, tumor stage, tumor grade or nodal status. In a survival analysis, p-mTOR IHC status of all CRC was unrelated to patient survival (P=0.702). In a multivariate analysis including pT, pN, tumor grade, tumor localization and p-mTOR expression, only pT, pN (both P<0.0001) and grade (P=0.0001) showed prognostic impact, but not tumor localization (P=0.9472) or p-mTOR expression (P=0.8879).

CONCLUSION: Our observations indicate that p-mTOR overexpression is abundant in CRC and linked to left-sided tumor localization. The high frequency and overexpression of p-mTOR is providing further rationale for targeting this pathway therapeutically in CRC patients. However, a prognostic role of p-mTOR overexpression in CRC could not be confirmed.