1. TTF1 expression in non-small cell lung carcinoma: association with TTF1 gene amplification and improved survival No conflicts of interest were declared.
- Author
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Department of Pathology, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA, Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USA ; SP and PW contributed equally to this study and should both be considered first authors., Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USA, Institute of Surgical Pathology, Department of Pathology, University Hospital of Zurich, Zurich, Switzerland, Department of Medical Oncology, Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA, USA ; Broad Institute of Harvard and M.I.T, Cambridge, MA, USA, Division of Thoracic Surgery, University Hospital of Zurich, Zurich, Switzerland, Department of Medical Oncology, Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA, USA ; Broad Institute of Harvard and M.I.T, Cambridge, MA, USA ; Department of Pathology, Harvard Medical School, Boston, MA, USA, Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USA ; Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USA., Perner, S., Wagner, P. L., Soltermann, A., LaFargue, C., Tischler, V., Weir, B. A., Weder, W., Meyerson, M., Giordano, T. J., Moch, H., Rubin, M. A., Department of Pathology, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA, Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USA ; SP and PW contributed equally to this study and should both be considered first authors., Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USA, Institute of Surgical Pathology, Department of Pathology, University Hospital of Zurich, Zurich, Switzerland, Department of Medical Oncology, Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA, USA ; Broad Institute of Harvard and M.I.T, Cambridge, MA, USA, Division of Thoracic Surgery, University Hospital of Zurich, Zurich, Switzerland, Department of Medical Oncology, Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA, USA ; Broad Institute of Harvard and M.I.T, Cambridge, MA, USA ; Department of Pathology, Harvard Medical School, Boston, MA, USA, Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USA ; Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USA., Perner, S., Wagner, P. L., Soltermann, A., LaFargue, C., Tischler, V., Weir, B. A., Weder, W., Meyerson, M., Giordano, T. J., Moch, H., and Rubin, M. A.
- Abstract
Acquired chromosomal aberrations play an important role in tumour 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. We asked whether TTF1 amplification is associated with increased TTF1 protein expression in NSCLCs, and whether TTF1 is associated with clinicopathological features, including patient survival. 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. We found TTF1 amplification in ???13% of adenocarcinomas (ACs) and in ???9% of squamous cell carcinomas (SCCs) and TTF1 amplification was associated with increased TTF1 protein expression. High-level TTF1 expression was significantly associated with smaller tumour size, female gender and longer overall survival only among ACs (median survival 82 versus 28 months; p = 0.002). On multivariate analysis, high TTF1 expression was an independent predictor of favourable prognosis in patients with AC [hazard ratio, 0.56 (95% CI 0.38???0.83); p = 0.008]. We conclude 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 favourable prognosis in AC. Copyright ?? 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
- Published
- 2009