OBJECTIVETo study p63 expression at mRNA transcript and protein levels in human lung cancers, including squamous cell lung carcinoma (SCC), adenocarcinoma, large cell lung carcinoma (LCLC) and small cell lung carcinoma (SCLC), or the corresponding metastatic foci. The relationship of p63 expression and alterations in p63 locus at chromosomal 3q27-29 was also determined.

METHODSp63 gene expression in 72 cases of SCC, adenocarcinoma, LCLC and SCLC was analyzed by cDNA microarray technology. Tissue microarray of specimens from 150 cases of primary lung cancer was prepared for immunohistochemical study for p63 protein. Possible chromosomal alterations at the p63 locus in 70 cases of primary lung cancer were studied by comparative genomic hybridization (CGH) technology.

RESULTSp63 mRNA transcript expression was significantly increased by more than 10-fold in SCC, as compared with that in other histologic subtypes including adenocarcinoma, LCLC and SCLC. p63 mRNA expression in metastatic foci was also remarkably higher than that in their primary tumors (P < 0.001). Immunostaining showed that p63 protein expression was observed in 94.64% of SCC, whereas only one lung adenocarcinoma (1.79%) was positive. Immunopositivity was also demonstrated in 2 of the 4 LCLC cases studied. None of the SCLC cases was positive. There was a statistically significant difference in p63 expression between pT1 and pT2 tumors (P < 0.05). The CGH results showed that overrepresentation of p63 locus at chromosomal 3q27-29 was a typical finding in SCC. p63 immunopositivity also correlated significantly with pronounced gains of p63 locus at chromosomal 3q27-q29 (P < 0.000 1), suggesting that strong expression of p63 in lung SCC was associated with increased gene amplification.

CONCLUSIONp63 may play a role in oncogenesis of human lung squamous cell carcinoma and development of metastasis.

Adenocarcinoma ; genetics ; metabolism ; Carcinoma, Large Cell ; genetics ; metabolism ; Carcinoma, Small Cell ; genetics ; metabolism ; Carcinoma, Squamous Cell ; genetics ; metabolism ; Chromosomes, Human, Pair 3 ; DNA-Binding Proteins ; Female ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Immunohistochemistry ; Lung Neoplasms ; genetics ; metabolism ; Male ; Oligonucleotide Array Sequence Analysis ; Phosphoproteins ; biosynthesis ; genetics ; Protein Array Analysis ; RNA, Messenger ; biosynthesis ; genetics ; Trans-Activators ; biosynthesis ; genetics ; Transcription Factors ; Tumor Suppressor Proteins