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

• DOI: 10.1097/jto.0b013e3181ce6604
• Publication Date: 2010-02-18T02:11:05Z
• Authors: Tony Dhillon; Francesco A. Mauri; Guido Bellezza; Lucio Cagini; Mattia Barbareschi; Bernard V. North; Michael J. Seckl
• Keywords: Pulmonary and Respiratory Medicine; Adult; Male; Lung Neoplasms; Adenocarcinoma; Protein Serine-Threonine Kinases; Immunoenzyme Techniques; 03 medical and health sciences; 0302 clinical medicine; Non-small cell lung cancer; Carcinoma, Non-Small-Cell Lung; Humans; Neoplasm Invasiveness; Aged; Neoplasm Staging; Aged, 80 and over; NSCLC; PROGNOSTIC FACTOR; EARLY STAGE; PULMONARY RESECTION; Intracellular Signaling Peptides and Proteins; Biomarker; Adenocarcinoma, Bronchiolo-Alveolar; Middle Aged; Prognosis; Carcinoma, Neuroendocrine; 3. Good health; Oncology; mTOR; Carcinoma, Squamous Cell; Carcinoma, Large Cell; Female

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.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.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).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.