Overexpression of the Mammalian Target of Rapamycin A Novel Biomarker for Poor Survival in Resected Early Stage Non-small Cell Lung Cancer

Introduction: The best hope of cure for patients with non-small cell lung cancer (NSCLC) is surgical resection. However, even in stage IA patients, 30% die within 5 years. Further improvements in survival require a biomarker(s), which defines the subset of these patients destined to do badly so that they could be targeted for additional therapies. Here, we investigate whether the immunohistochemical expression of a key kinase implicated in lung cancer biology, the mammalian target of rapamycin (mTOR) can predict survival outcome in patients with early stage resected NSCLC. Materials and Methods: One hundred thirty-four patients with resected early stage (IA-IIB) NSCLC were pathologically reviewed centrally before staining for mTOR. Multiple variables including age, sex, stage, angioinvasion, lymph node status, and mTOR staining were assessed by univariate and multivariate analyses. Results: Stage (p = 0.044), lymph node status (p = 0.049), angioinvasion (p = 0.017), and mTOR staining (p = 0.007) were significant univariate predictors of poor survival. However, only angioinvasion (p = 0.016) and mTOR staining (p = 0.046) remained significant after multivariate analysis. Moreover, mTOR staining was the only variable to predict poor outcome in patients who either had negative lymph nodes (p = 0.016) or were stage IA (p = 0.0016). Conclusions: The mTOR staining provides a new biomarker for poor outcome in early stage NSCLC and could enable resected stage IA patients to be selected for novel therapies possibly with an mTOR inhibitor.