Overexpression of the mammalian target of rapamycin (mTOR) and angioinvasion are poor prognostic factors in early stage NSCLC: A verification study

Gately, K., Al-Alao, B., Dhillon, T., Mauri, F., Cuffe, S., Seckl, M., & O'Byrne, Kenneth J. (2012) Overexpression of the mammalian target of rapamycin (mTOR) and angioinvasion are poor prognostic factors in early stage NSCLC: A verification study. Lung Cancer, 75(2), pp. 217-222.

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Abstract

Background: A recent study by Dhillon et al. [12], identified both angioinvasion and mTOR as prognostic biomarkers for poor survival in early stage NSCLC. The aim of this study was to verify the above study by examining the angioinvasion and mTOR expression profile in a cohort of early stage NSCLC patients and correlate the results to patient clinico-pathological data and survival.

Methods: Angioinvasion was routinely recorded by the pathologist at the initial assessment of the tumor following resection. mTOR was evaluated in 141 early stage (IA-IIB) NSCLC patients (67 - squamous; 60 - adenocarcinoma; 14 - others) using immunohistochemistry (IHC) analysis with an immunohistochemical score (IHS) calculated (% positive cells × staining intensity). Intensity was scored as follows: 0 (negative); 1+ (weak); 2+ (moderate); 3+ (strong). The range of scores was 0-300. Based on the previous study a cut-off score of 30 was used to define positive versus negative patients. The impact of angioinvasion and mTOR expression on prognosis was then evaluated.

Results: 101 of the 141 tumors studied expressed mTOR. There was no difference in mTOR expression between squamous cell carcinoma and adenocarcinoma. Angioinvasion (p= 0.024) and mTOR staining (p= 0.048) were significant univariate predictors of poor survival. Both remained significant after multivariate analysis (p= 0.037 and p= 0.020, respectively).

Conclusions: Our findings verify angioinvasion and mTOR expression as new biomarkers for poor outcome in patients with early stage NSCLC. mTOR expressing patients may benefit from novel therapies targeting the mTOR survival pathway. © 2011 Elsevier Ireland Ltd.

Impact and interest:

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ID Code: 65054
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: Angioinvasion, Early stage NSCLC, Immunohistochemistry (IHC), Mammalian target of rapamycin (mTOR), MTOR inhibitors, Poor prognostic factor, biochemical marker, everolimus, mammalian target of rapamycin, mammalian target of rapamycin inhibitor, ridaforolimus, temsirolimus, adult, aged, article, cancer invasion, cancer staging, clinical feature, correlation analysis, drug targeting, female, histopathology, human, human tissue, immunohistochemistry, lung adenocarcinoma, lung non small cell cancer, lung squamous cell carcinoma, major clinical study, male, prediction, priority journal, prognosis, protein expression, scoring system, survival rate, tissue microarray, Aged, 80 and over, Blood Vessels, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Middle Aged, Neoplasm Invasiveness, Neoplasm Staging, TOR Serine-Threonine Kinases
DOI: 10.1016/j.lungcan.2011.06.012
ISSN: 0169-5002
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 Elsevier
Deposited On: 04 Dec 2013 00:19
Last Modified: 19 Dec 2013 02:44

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