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[Cancer Research 63, 7113-7121, November 1, 2003]
© 2003 American Association for Cancer Research

Regular Articles

Significance of p63 Amplification and Overexpression in Lung Cancer Development and Prognosis1

Pierre P. Massion2, Peter M. Taflan, S. M. Jamshedur Rahman, Pinar Yildiz, Yu Shyr, Mary E. Edgerton, Matthew D. Westfall, John R. Roberts, Jennifer A. Pietenpol, David P. Carbone and Adriana L. Gonzalez

Department of Medicine [P. P. M., P. M. T., S. M. J. R., P. Y., D. P. C.], Biostatistics Shared Resource [Y. S.], The Vanderbilt Ingram Cancer Center, Molecular Profiling and Data Mining Shared Resource [M. E. E.], and Departments of Pathology [M. E. E., A. L. G.], Biochemistry [M. D. W., J. A. P.], and Surgery [J. R. R.], The Vanderbilt Ingram Comprehensive Cancer Center, Vanderbilt University, School of Medicine, Nashville Veterans Affairs Medical Center [P. P. M.], Nashville, Tennessee 37232-6838

The fight against lung cancer is greatly compromised by the lack of effective early detection strategies. Genomic abnormalities and specifically the amplification of chromosomal region 3q26-3qter in lung cancer represent a major signature of neoplastic transformation. Here, we address the significance of p53 homologue p63 mapping to 3q27 in lung tumorigenesis. We analyzed p63 gene copy number (CN) by fluorescence in situ hybridization and expression by immunohistochemistry in tissue microarrays of 217 non-small cell lung cancers (NSCLCs) and correlated them with survival. We additionally characterized our findings in a subset of 24 NSCLCs by reverse transcription-PCR and Western blotting. We analyzed p63 CN and protein expression in 41 preinvasive squamous lesions. The p63 genomic sequence was amplified in 88% of squamous carcinomas, in 42% of large cell carcinomas, and in 11% of adenocarcinomas of the lung. The predominant splice variant of p63 expressed was {Delta}Np63{alpha}. Western analyses revealed {Delta}Np63{alpha} expression in normal bronchus and squamous carcinomas but not in normal lung or in adenocarcinomas. Furthermore, p63genomic amplification and protein staining intensity associated with better survival. We found a significant increase in CN in preinvasive lesions graded severe dysplasia or higher. Our data demonstrate that there is early and frequent genomic amplification of p63 in the development of squamous carcinoma of the lung and that patients with NSCLC showing amplification and overexpression of p63 have prolonged survival. These observations suggest that p63 genomic amplification has an early role in lung tumorigenesis and deserves additional evaluation as a biomarker for lung cancer progression.




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Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2003 by the American Association for Cancer Research.