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Telomerase activity and expression of its RNA component in cervical lesions
Author(s) -
Yashima Kazuo,
Ashfaq Raheela,
Nowak Jan,
Gruenigen Vivian Von,
Milchgrub Sara,
Rathi Asha,
AlboresSaavedra Jorge,
Shay Jerry W.,
Gazdar Adi F.
Publication year - 1998
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/(sici)1097-0142(19980401)82:7<1319::aid-cncr15>3.0.co;2-9
Subject(s) - telomerase , medicine , pathology , carcinoma in situ , pathogenesis , hpv infection , polymerase chain reaction , biopsy , cancer research , carcinoma , cervical cancer , cancer , biology , gene , biochemistry
BACKGROUND The authors investigated telomerase enzyme activity and expression of its RNA component (hTR) during the multistage pathogenesis of cervical carcinomas, and correlated activation with histopathologic findings and human papillomavirus (HPV) infection. METHODS The authors analyzed 180 cervical specimens for enzyme activity, and analyzed hTR expression in an additional 55 samples from archival carcinoma cases. Polymerase chain reaction‐based assays were used to determine telomerase enzyme activity and HPV infection, whereas a radioactive in situ assay was used for hTR expression. RESULTS Telomerase enzyme activity 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 were low in all preinvasive specimens except for three samples of HSIL with high activity. Although 21% of the brush samples had evidence of HPV infection, there was no obvious correlation between telomerase activity and HPV status. hTR expression was low in normal squamous/glandular epithelium and LSIL lesions, in which it was limited to the basal cells. In squamous and glandular in situ and invasive carcinomas, increased and dysregulated hTR expression was observed, although heterogeneity was noted. Intense focal up‐regulation of hTR expression occurred in a subset of in situ lesions. CONCLUSIONS Increased frequency and dysregulation of telomerase activation is correlated with increasing severity of histopathologic changes, but not with HPV infection. Whether dysregulated activity is a prognostic marker for development of invasive carcinoma remains to be determined. Cancer 1998;82:1319‐27. © 1998 American Cancer Society.