Overexpression of the mammalian target of rapamycin: a novel biomarker for poor survival in resected early stage non-small cell lung cancer.

Abstract

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.

• Authors: Tony Dhillon, Francesco A Mauri, Guido Bellezza, Lucio Cagini, Mattia Barbareschi, Bernard V North, Michael J Seckl
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 5 Issue 3 Pg. 314-9 (Mar 2010) ISSN: 1556-1380 [Electronic] United States
• PMID: 20093977 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Intracellular Signaling Peptides and Proteins
• MTOR protein, human
• Protein Serine-Threonine Kinases
• TOR Serine-Threonine Kinases

Topics

• Adenocarcinoma (metabolism, mortality, pathology)
• Adenocarcinoma, Bronchiolo-Alveolar (metabolism, mortality, pathology)
• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Large Cell (metabolism, mortality, pathology)
• Carcinoma, Neuroendocrine (metabolism, mortality, pathology)
• Carcinoma, Non-Small-Cell Lung (metabolism, mortality, pathology)
• Carcinoma, Squamous Cell (metabolism, mortality, pathology)
• Female
• Humans
• Immunoenzyme Techniques
• Intracellular Signaling Peptides and Proteins (metabolism)
• Lung Neoplasms (metabolism, mortality, pathology)
• Male
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Staging
• Prognosis
• Protein Serine-Threonine Kinases (metabolism)
• Survival Rate
• TOR Serine-Threonine Kinases
• Tissue Array Analysis