Telomerase in (pre)neoplastic cervical disease

This study was performed to determine upregulation of the human telomerase RNA component (hTR) and mRNA of the catalytic subunit of telomerase (hTERT) in (pre)malignant cervical lesions, to analyze possible intralesional hete rogeneity of hTR expression, and to relate hTR and hTERT mRNA levels to tel omerase activity levels and human papillomavirus (HPV) typing. hTR expressi on was determined by in situ hybridization (ISH) on paraffin-embedded secti ons, obtained from patients with cervical intraepithelial neoplasia (CIN) I -III or cervical cancer and from normal controls. hTR and hTERT mRNA expres sion were determined by semiquantitative rt-PCR on frozen samples from the same lesions. Data on telomerase activity and HPV were obtained from a prev ious study. hTR expression as determined by ISH was observed in 0 of 8 norm al cervices, 1 of 14 CIN I, 15 of 28 CIN II, 21 of 30 CIN III, and 16 of 18 cervical cancer specimens. In general, hybridization patterns for hTR expr ession were homogeneous throughout the lesion. Frequency of hTR expression was related to grade of CIN/cervical cancer (P < .001). hTR expression, as determined by rt-PCR, was detected in 8 of 8 normal cervices, 2 of 2 CIN I, 12 of 14 CIN II, 23 of 23 CIN III, and 16 of 17 cervical cancer specimens. hTERT mRNA was detected in 1 of 8 normal cervices, 1 of 2 CIN I, 5 of 14 C IN II, 14 of 23 CIN III, and 11 of 17 cervical cancer specimens. hTR as det ermined by rt-PCR was not related to grade of CIN/cervical cancer, whereas hTERT mRNA expression was related to grade of CIN/cervical cancer (P < .01) . hTR expression, as determined by ISH and hTERT mRNA expression by rt-PCR, were related to telomerase activity levels (P < .001, P < .05, respectivel y) and presence of oncogenic types of HPV (both P < .05). Our data show fre quent upregulation of hTR and hTERT mRNA expression in CIN lesions, which a ppear to occur earlier than induction of telomerase activity. The fact that semiquantitative hTERT mRNA as well as hTR levels are related to telomeras e activity levels illustrates that in (pre)malignant cervical lesions upreg ulation of both telomerase components may be important for functional telom erase. HUM PATHOL 31:1304-1312. Copyright (C) 2000 by W.B. Saunders Company .