Telomerase activity and expression of its RNA component in cervical lesions

Kazuo Yashima, Raheela Ashfaq, Jan Nowak, Vivian Von Gruenigen, Sara Milchgrub, Asha Rathi, Jorge Albores-Saavedra, Jerry W. Shay, Adi F. Gazdar

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1319-1327
Number of pages9
JournalCancer
Volume82
Issue number7
DOIs
StatePublished - Apr 1 1998

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Telomerase
Papillomavirus Infections
RNA
Enzymes
Carcinoma
Human Activities
Epithelium
Carcinoma in Situ
Up-Regulation
Polymerase Chain Reaction
Squamous Intraepithelial Lesions of the Cervix

Keywords

  • Cervical carcinoma
  • Human papillomavirus
  • In situ hybridization
  • Preneoplasia
  • Telomerase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Telomerase activity and expression of its RNA component in cervical lesions. / Yashima, Kazuo; Ashfaq, Raheela; Nowak, Jan; Von Gruenigen, Vivian; Milchgrub, Sara; Rathi, Asha; Albores-Saavedra, Jorge; Shay, Jerry W.; Gazdar, Adi F.

In: Cancer, Vol. 82, No. 7, 01.04.1998, p. 1319-1327.

Research output: Contribution to journalArticle

Yashima, K, Ashfaq, R, Nowak, J, Von Gruenigen, V, Milchgrub, S, Rathi, A, Albores-Saavedra, J, Shay, JW & Gazdar, AF 1998, 'Telomerase activity and expression of its RNA component in cervical lesions', Cancer, vol. 82, no. 7, pp. 1319-1327. https://doi.org/10.1002/(SICI)1097-0142(19980401)82:7<1319::AID-CNCR15>3.0.CO;2-9
Yashima, Kazuo ; Ashfaq, Raheela ; Nowak, Jan ; Von Gruenigen, Vivian ; Milchgrub, Sara ; Rathi, Asha ; Albores-Saavedra, Jorge ; Shay, Jerry W. ; Gazdar, Adi F. / Telomerase activity and expression of its RNA component in cervical lesions. In: Cancer. 1998 ; Vol. 82, No. 7. pp. 1319-1327.
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AU - Yashima, Kazuo

AU - Ashfaq, Raheela

AU - Nowak, Jan

AU - Von Gruenigen, Vivian

AU - Milchgrub, Sara

AU - Rathi, Asha

AU - Albores-Saavedra, Jorge

AU - Shay, Jerry W.

AU - Gazdar, Adi F.

PY - 1998/4/1

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N2 - 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.

AB - 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.

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KW - Human papillomavirus

KW - In situ hybridization

KW - Preneoplasia

KW - Telomerase

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