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Loss of heterozygosity and human telomerase reverse transcriptase (hTERT) expression in bronchial mucosa of heavy smokers
Author(s) -
Capkova Linda,
Kalinova Marketa,
Krskova Lenka,
Kodetova Daniela,
Petrik Frantisek,
Trefny Martin,
Musil Jaromir,
Kodet Roman
Publication year - 2007
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.22683
Subject(s) - telomerase reverse transcriptase , pathology , dysplasia , metaplasia , carcinogenesis , loss of heterozygosity , squamous metaplasia , medicine , lung cancer , telomerase , malignant transformation , carcinoma , biology , cancer , epithelium , gene , allele , biochemistry
BACKGROUND Lung carcinogenesis is a multistep process of accumulation of genetic changes, including loss of heterozygosity (LOH), and precedes phenotypic transformation of the bronchial mucosa. The activity of telomerase, correlating with the hTERT mRNA expression, is detectable in a majority of neoplasms. In this study, the frequency of LOH and hTERT expression in bronchial mucosa of heavy smokers in bronchoscopic biopsies was analyzed. METHODS LOH was examined in 122 bronchial specimens from 81 smokers (67 normal mucosa/bronchitis, 12 squamous metaplasia, 28 dysplasia, 15 bronchogenic carcinoma specimens) by polymerase chain reaction (PCR) and capillary electrophoresis by using 7 fluorescence‐labeled markers matching 5 chromosomal regions. hTERT expression was analyzed in 87 specimens (45 normal mucosa/bronchitis, 12 squamous metaplasia, 18 dysplasia, 12 bronchogenic carcinoma specimens) by real‐time quantitative reverse‐transcription PCR. RESULTS LOH was detected in at least 1 chromosomal region in 51 of 122 (41.8%) specimens; the incidence in normal bronchial mucosa and preneoplastic lesions was similar (20%–40%); a substantial rise (87%) occurred in carcinomas. The median normalized hTERT N values were 6.67 in normal epithelium/chronic bronchitis, 18.38 in squamous metaplasia, 13.31 in epithelial dysplasia, and 75.46 in carcinomas. These results were significantly different ( P = .0036). With an increasing number of LOH, the median value of hTERT N expression rose, but hTERT was expressed also in tissue samples without any LOH detection. CONCLUSIONS Results indicated that hTERT expression, together with LOH, represent early events in lung carcinogenesis, as both were detected in precancerous lesions and in normal epithelium of heavy smokers. Cancer 2007. © 2007 American Cancer Society.