TELOMERASE ACTIVITY AND EXPRESSION OF ITS RNA COMPONENT IN CERVICAL LESIONS

BACKGROUND. The authors investigated telomerase enzyme activity and ex pression of its RNA component (hTR) during the multistage pathogenesis of cervical carcinomas, and correlated activation with histopathologi c findings and human papillomavirus (HPV) infection. METHODS, The auth ors analyzed 180 cervical specimens for enzyme activity, and analyzed hTR expression in an additional 55 samples from archival carcinoma cas es. Polymerase chain reaction-based assays were used to determine telo merase enzyme activity and HPV infection, whereas a radioactive in sit u assay was used for hTR expression. RESULTS, Telomerase enzyme activi ty was present in some samples of histologically normal epithelium (18 of 138; 13%) and low grade squamous intraepithelial lesions (LSIL) (7 of 21; 33%), and in most high grade squamous intraepithelial lesions (HSIL) (13 of 21; 62%). The relative levels of telomerase activity wer e low in all preinvasive specimens except for three samples of HSIL wi th high activity. Although 21% of the brush samples had evidence of HP V infection, there was no obvious correlation between telomerase activ ity and HPV status. hTR expression was low in normal squamous/glandula r epithelium and LSIL lesions, in which it was limited to the basal ce lls. In squamous and glandular in situ and invasive carcinomas, increa sed and dysregulated hTR expression was observed, although heterogenei ty was noted. Intense focal up-regulation of hTR expression occurred i n a subset of in situ lesions. CONCLUSIONS, Increased frequency and dy sregulation of telomerase activation is correlated with increasing sev erity of histopathologic changes, but not with HPV infection. Whether dysregulated activity is a prognostic marker for development of invasi ve carcinoma remains to be determined. (C) 1998 American Cancer Societ y.