TTF1 Expression in Non-Small Cell Lung Carcinoma: Association with TTF1 Gene Amplification and Improved Survival
PL Wagner, S Perner, A Soltermann, CL LaFargue, V Tischler, BA Weir, W Weder, M Meyerson, TJ Giordano, H Moch, MA Rubin. Weill Medical College of Cornell University, New York, NY; University Hospital of Zurich, Zurich, Switzerland; University of Zurich, Zurich, Switzerland; University of Michigan, Ann Arbor, MI; Dana Farber Cancer Institute, Boston, MA
Background: Acquired chromosomal aberrations play an important role in tumor development and progression. Such genetic alterations occur in a significant proportion of non-small cell lung carcinomas (NSCLCs), and include amplification of 14q13.3, which contains the TTF1 gene. The aim of our study was to determine whether TTF1 amplification is associated with increased TTF1 protein expression in NSCLCs, and whether TTF1 is associated with clinicopathologic features including patient survival.
Design: We used a FISH assay and quantitative immunohistochemical staining to interrogate a population-based cohort of 538 NSCLCs from Swiss patients for TTF1 amplification and protein expression. Amplification status and protein expression levels were compared with patient and tumor characteristics, including overall survival using Kaplan-Meier and Cox multivariate regression analysis.
Results: TTF1 amplification was found in 13% of adenocarcinomas (ACs) and in 9% of squamous cell carcinomas (SCCs). Amplification was associated with increased TTF1 protein expression. High-level TTF1 expression was significantly associated with smaller tumor size, female gender, and longer overall survival only among ACs (median survival 82 vs. 28 months; p=0.002). On multivariate analysis, high TTF1 expression was an independent predictor of favorable prognosis in patients with AC (hazard ratio 0.56 [95%CI 0.38-0.83]; p=0.008).
Conclusions: We are among the first to demonstrate that TTF1 amplification is a mechanism of high-level TTF1 expression in a subset of NSCLCs. When expressed at high levels, this routinely used diagnostic marker is also an independent biomarker of favorable prognosis in AC.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 239, Tuesday Afternoon