High expression of mammalian target of rapamycin is associated with better outcome for patients with early stage lung adenocarcinoma

Valsamo K. Anagnostou, Gerold Bepler, Konstantinos N. Syrigos, Lynn Tanoue, Scott Gettinger, Robert J. Homer, Daniel Boffa, Frank Detterbeck, David L. Rimm

Research output: Contribution to journalArticle

Abstract

Purpose: Mammalian target of rapamycin (mTOR) is a key kinase downstream of phosphoinositide 3-kinase (PI3K)/AKT predominantly involved in translational control in the presence of nutrients and energy. Despite the well known role of mTORi n carcinogenesis, its prognostic potential inlung cancer has not beeninvestigated.Here,we quantitatively assessedmTORprotein expression in two large data sets to investigate the impact ofmTORexpression on patient survival. Experimental Design: Automated quantitative analysis (AQUA), a fluorescent-based method for analysis of in situ protein expression, was used to assessmTORexpression in a training cohort of 167 lung cancer patients. An independent cohort of 235 lung cancer patients (from a second institution) was used for validation. Results: Tumors expressed mTOR in the cytoplasmin 56% and 50% of the cases in training and validation cohorts, respectively; mTORe xpression was not associated with standard clinical or pathologic characteristics. Patients with high mTORe xpression had a longer median overall survival comparedwith the lowexpressers (52.7 versus 38.5months; log rank P = 0.06), whichwas more prominent in the adenocarcinoma group (55.7 versus 38.88 months; log rank P = 0.018). Multivariate analysis revealed an independent lower risk of death for adenocarcinoma and adenocarcinoma stage IA patients with mTOR-expressing tumors (hazard ratio, 0.48; 95% confidence interval, 0.24-0.98; P = 0.04, and hazard ratio, 0.12; 95% confidence interval, 0.03-0.72; P = 0.019, respectively). Conclusions: mTORex pression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of lung adenocarcinoma patients as well as incorporation of mTORin to clinical decisions.

Original languageEnglish (US)
Pages (from-to)4157-4164
Number of pages8
JournalClinical Cancer Research
Volume15
Issue number12
DOIs
StatePublished - Jun 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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