Clinicopathological correlations of mTOR and pAkt expression in non-small cell lung cancer.

ABSTRACT

The Akt/mammalian target of rapamycin (mTOR) pathway is up-regulated in many human cancers, and agents targeting the mTOR pathway are in various stages of clinical development and application. Expression of pAkt and mTOR was studied by immunohistochemical analysis of 574 surgically resected non-small cell lung cancer (NSCLC) specimens on a tissue microarray. The results were correlated with clinicopathological features. Expression of mTOR showed a strong correlation with the expression of pAkt (p < 0.001) and was significantly associated with female gender, tumor size of ≤3 cm, adenocarcinoma (ADC), non-smoker status, and lower pathological stage. Expression of pAkt was correlated with older age (≥65), ADC, non-smoker status, and lower T stage. Univariate survival analysis revealed that the mTOR- and pAkt-positive group had a significantly longer cancer-specific survival than the mTOR- and pAkt-negative group (p = 0.038 and 0.024, respectively). Coexpression of pAkt and mTOR correlated with better prognosis than either single- or double-negative pAkt and mTOR groups (p = 0.016). However, multivariate analysis proved that mTOR and pAkt expression are not independent prognostic factors for cancer-specific survival. Expression of pAkt and mTOR expression is more significantly associated with ADC than squamous cell carcinoma. Although pAkt/mTOR expression is not an independent prognostic marker, expression of these proteins is associated with better prognosis.