Telomerase activity and expression of its RNA component in cervical lesions.
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.
Yashima
K
K
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas 75235-8593, USA.
Ashfaq
R
R
Nowak
J
J
Von Gruenigen
V
V
Milchgrub
S
S
Rathi
A
A
Albores-Saavedra
J
J
Shay
J W
JW
Gazdar
A F
AF
D000230:Adenocarcinoma / Q000150:complications / Q000201:enzymology / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000201:enzymology / Q000235:genetics; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D018655:Lymphocyte Count; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications; D012313:RNA / Q000032:analysis; D019098:Telomerase / Q000378:metabolism*; D014412:Tumor Virus Infections / Q000150:complications; D002583:Uterine Cervical Neoplasms / Q000150:complications / Q000201:enzymology* / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000150:complications / Q000201:enzymology / Q000235:genetics
D012313:RNA; D019098:Telomerase