Increased telomerase activity and elevated hTERT mRNA expression during multistage carcinogenesis of squamous cell carcinoma of the lung

Abstract

BACKGROUND. Telomerase activation is believed to be play a critical role in the immortalization of cells and carcinogenesis. Telomerase activity is undetectable in normal somatic cells (except for those cells undergoing proliferation) but is expressed in the majority of human tumors including lung carcinoma. The expression of hTERT mRNA has been found to be correlated with telomerase activity. In the current study, the authors analyzed telomerase activity and hTERT mRNA expression in preinvasive bronchial lesions using biopsy specimens obtained by fluorescence bronchoscopy. METHODS. The authors studied 150 bronchial biopsy specimens obtained by fluorescence bronchoscopy. The intensity of telomerase activity was determined by the fluorescence-based telomeric repeat amplification protocol method in 74 bronchial biopsy specimens (22 normal bronchial epithelium or bronchitis cases, 15 squamous metaplasia cases, 23 dysplasia cases, and 14 squamous cell carcinoma cases), and the level of hTERT mRNA was analyzed in another 76 specimens (24 normal bronchial epithelium or bronchitis cases, 15 squamous metaplasia cases, 20 dysplasia cases, and 17 squamous cell carcinoma cases) by real-time polymerase chain reaction. RESULTS. The mean values (± the standard deviation [SD]) of telomerase activity in normal bronchial epithelium or bronchitis, squamous metaplasia, dysplasia, and squamous cell carcinoma cases were 6.2 ± 7.5, 13.9 ± 14.8, 18.5 ± 20.8, and 54.5 ± 22.3 U/μg protein, respectively. The upper limit of telomerase activity in normal bronchial epithelium or bronchitis was 21 U/μg protein (mean + 2SD). It is interesting to note that, 5 of 15 squamous metaplasia biopsies (33%), 8 of 23 dysplasia biopsies (35%), and all squamous cell carcinoma biopsies (100%) exhibited levels of telomerase activity that were > 21 U/μg protein. The mean levels of hTERT mRNA in normal bronchial epithelium or bronchitis, squamous metaplasia, dysplasia, and squamous cell carcinoma cases were 891 ± 840, 1936 ± 1704, 3019 ± 2607, and 12965 ± 18008 copies/ μg total RNA, respectively. Telomerase activity and hTERT mRNA expression were found to increase in proportion to the severity of histologic change from normal bronchial epithelium or bronchitis to squamous cell carcinoma. CONCLUSIONS. These results suggest that an increase in telomerase activity and hTERT mRNA expression are features of the early stages of the development of squamous cell carcinoma of the lung, with strong telomerase activity and hTERT mRNA expression being prominent during the latter stages. © 2001 American Cancer Society.