Telomerase activity and expression of its RNA component in cervical lesions

Yashima, Kazuo; Ashfaq, Raheela; Nowak, Jan A.; Gruenigen, Vivian von; Milchgrub, Sara; Rathi, Asha; Albores‐Saavedra, Jorge; Shay, Jerry W.; Gazdar, Adi F.

doi:10.1002/(sici)1097-0142(19980401)82:7<1319::aid-cncr15>3.3.co;2-5

Cited by 20 publications

(39 citation statements)

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“…These findings are in accordance with earlier reports (Zheng et al, 1997), which suggest telomerase activation as an early event occurring during cervical neoplastic transformation and HPV infection (Yashima et al, 1998). Consequently, monitoring telomerase activity could also have potential prognostic significance.…”

Section: Discussionsupporting

confidence: 93%

Telomerase activity as an adjunct to high-risk human papillomavirus types 16 and 18 and cytology screening in cervical cancer

et al. 2006

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Telomerase is a ribonucleoprotein comprising an RNA template, the telomerase-associated protein and its catalytic subunit, human telomerase reverse transcriptase (hTERT). Telomerase activation is a critical step in cellular immortalisation and development of cancer. Enhanced telomerase activity has been demonstrated in cervical cancer. In the present study telomerase activity and hTERT mRNA expression were evaluated and correlated with the presence of human papillomavirus (HPV) infection and cytological changes in the cervical lesions. Telomerase activity was assayed by telomeric repeat amplification protocol, hTERT mRNA expression by reverse transcriptase polymerase chain reaction and presence of high risk HPV (HR-HPV) infection by polymerase chain reaction. Out of 154 cervical samples of different cytology, 90 (58.44%) were positive for HR-HPV types 16/18, while among 55 normal cervical scrapes, 10 (18.18%) were HPV DNA positive. All 59 invasive cancer samples showed a very high telomerase activity. Among dysplasia, seven (63.6%) mild dysplasia, 18 (100%) of moderate, 20 (100%) of severe dysplasia and 6 (100%) carcinoma in situ (CIS) samples were positive with mild to moderate to high to very high telomerase activity respectively. Seven (12.7%) samples of apparently normal cervical scrapes were weakly positive for telomerase activity. We observed a good correlation (Po0.001) between telomerase activity and HR-HPV 16/18 positivity with a sensitivity of 88.1% for HPV and 100% for telomerase activity. It is suggested that telomerase activity may be used as an adjunct to cytology and HPV DNA testing in triaging women with cervical lesions.

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Section: Discussionsupporting

confidence: 93%

Telomerase activity as an adjunct to high-risk human papillomavirus types 16 and 18 and cytology screening in cervical cancer

et al. 2006

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“…Reaction products were electrophoresed in a 10% nondenaturing polyacrylamide gel and visualized using a Molecular Dynamics Phosphorimager screen Bednarek et al (1997) reported on six DCIS tumors, all of which showed telomerase activity, Tsao et al (1997) reported that nine out of 12 DCIS were telomerase positive. Yashima et al (1998) reported that 11 out of 12 DCIS cases were telomerase positive, while Poremba et al (1998) reported ten out of 17 positive cases.…”

Section: Discussionmentioning

confidence: 99%

“…It is not known, however, when in neoplastic progression this activation occurs. Previous reports have detected telomerase activity in anywhere form 60 ± 100% of ductal carcinoma in situ (DCIS) of the breast (Bednarek et al, 1997;Poremba et al, 1998;Tsao et al, 1997;Yashima et al, 1998), but the studies have been limited by small sample sizes (n=5 ± 17). The large proportion of invasive breast cancers that are telomerase positive (Carey et al, 1998) also suggest that telomerase activation may occur in early stages of the disease.…”

Section: Introductionmentioning

confidence: 99%

Telomerase activity in ductal carcinoma in situ and invasive breast cancer

et al. 1999

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The increasing number of breast carcinoma in situ detected by screening procedures makes it imperative to develop improved markers to stratify the risk of invasive cancer. Telomerase is detectable in invasive cancer, but not in normal tissues. We have microdissected frozen tissue blocks containing both DCIS and invasive cancer to assay the telomerase activity of these two lesions. The 46 available cases of concurrent DCIS and invasive breast cancer resulted in 43 DCIS samples and 38 invasive cancer samples adequate for analysis. Seventy per cent of the DCIS and all invasive cancer samples tested had detectable telomerase activity. In addition, we analysed telomerase activity in ten cases of DCIS that were not associated with invasive cancer, and detected telomerase activity in seven (70%). Mixing experiments showed no evidence of telomerase inhibitors in telomerase negative samples. Furthermore, periductal in¯ammatory in®ltrates were shown to be a potential confounding source of telomerase activity. Since DCIS lesions appear to be heterogeneous with respect to telomerase activity, and telomerase activation appears to precede the development of invasive cancer, telomerase activity may be a useful adjunct in stratifying the risk of developing invasive breast cancer in patients with DCIS.

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“…Telomerase in cervical dysplasia and cancer EA Jarboe et al using GP5/GP6 consensus sequence PCR, Yashima et al (1998) detected HPV types 16/18 in 11 of 13 HSIL cervical biopsies, including four biopsies that were positive for both telomerase expression and HPV DNA. Furthermore, the expression of telomerase correlated with the intensity of HPV 16/18 E6/E7 oncogene expression, as determined by in situ hybridization in high grade dysplasia and SCC (Riethdorf et al, 2001).…”

Section: Oncogenementioning

confidence: 96%

“…In situ hybridization has demonstrated that hTR is largely restricted to the basal and parabasal cell layers of ectocervical mucosa, metaplastic squamous epithelium, or LSIL, although focal expression has also been observed in some histologically normal endocervical glands (Yashima et al, 1998;Frost et al, 2000). By contrast, hTR was detected throughout all layers of the lesional mucosa in moderate dysplasia, severe dysplasia, and in carcinoma in situ (Yashima et al, 1998;Frost et al, 2000;Wisman et al, 2000). Nakano et al (1998) demonstrated that hTR and hTERT mRNA are colocalized in cervical SCCs as well as in benign and dysplastic cervical mucosa biopsy specimens.…”

Section: Histologic Localization Of Telomerasementioning

confidence: 99%

Analysis of telomerase as a diagnostic biomarker of cervical dysplasia and carcinoma

et al. 2002

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Telomerase activity and expression of its RNA component in cervical lesions

Abstract: 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.

Cited by 20 publications

References 0 publications

Telomerase activity as an adjunct to high-risk human papillomavirus types 16 and 18 and cytology screening in cervical cancer

Telomerase activity as an adjunct to high-risk human papillomavirus types 16 and 18 and cytology screening in cervical cancer

Telomerase activity in ductal carcinoma in situ and invasive breast cancer

Analysis of telomerase as a diagnostic biomarker of cervical dysplasia and carcinoma

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