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Role of P63 Amplification and Overexpression in Lung Cancer Development* FREE TO VIEW

Pierre P. Massion, MD; Peter M. Taflan, BS; S.M. Jamshedur Rahman, PhD; Pinar Yildiz, MD; Yu Shyr; David P. Carbone, MD; Adriana L. Gonzalez
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*From the Division of Allergy, Pulmonary and Critical Care Medicine (Drs. Massion, Yildiz, and Rahman, and Mr. Taflan); Department of Biostatistics (Mr. Shyr); Department of Medicine (Dr. Carbone); and the Vanderbilt Ingram Comprehensive Cancer Center (Ms. Gonzalez), Nashville, TN.

Correspondence to: Pierre P. Massion, MD, Vanderbilt Ingram Comprehensive Cancer Center, 2200 Pierce Ave, Preston Research Bldg 640, Nashville, TN 37232-6838.

Chest. 2004;125(5_suppl):102S. doi:10.1378/chest.125.5_suppl.102S-a
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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 homolog p63 mapping to 3q27 in lung tumorigenesis.

We analyzed p63 gene copy number (CN) by fluorescence in situ hybridization and its expression by immunohistochemistry in tissue microarrays of 217 non-small cell lung cancers (NSCLCs), and correlated it with survival. We further characterized our findings in a subset of 24 NSCLCs by reverse transcription-polymerase chain reaction and Western blotting. We analyzed the p63 CNs and protein expression in 41 preinvasive squamous lesions.

The p63 genomic sequence was amplified in 88% of squamous cell carcinomas, in 42% of large cell carcinomas, and in 11% of adenocarcinomas of the lung. The predominant splice variant of p63 expressed was DNp63a. Western blot analyses revealed DNp63a expression in the normal bronchus and squamous carcinomas, but not in the normal lung or in adenocarcinomas. Furthermore, p63 genomic amplification and protein staining intensity was associated with better survival. We found a significant increase in the CNs in preinvasive lesions that were graded as being severe dysplasia or higher.

Our data demonstrate the early and frequent genomic amplification of p63 in the development of squamous cell carcinoma of the lung, and that patients with NSCLC showing amplification and overexpression of p63 have a prolonged survival. These observations suggest that p63 genomic amplification has a role early in lung tumorigenesis and deserves further evaluation as a biomarker for lung cancer progression.

Abbreviations: CN = copy number; NSCLC = non-small cell lung cancer




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