Application of hTERC in thinprep samples with mild cytologic abnormality and HR-HPV positive

Women's Reproductive Health Laboratory of Zhejiang Province, China.
Gynecologic Oncology (Impact Factor: 3.77). 10/2010; 120(1):73-83. DOI: 10.1016/j.ygyno.2010.10.007
Source: PubMed


Amplification of hTERC is found to be an important genetic event in the progression from cervical dysplasia to cervical cancer. The hTERC value in predicting high-grade cervical intraepithelial neoplasia (CIN) or squamous cell carcinoma (SCC), in high-risk HPV (HR-HPV) positive thinprep samples with atypical squamous cells (ASC) or a low-grade squamous intraepithelial lesion (LSIL) was explored in this study.
A total of 300 thinprep cytology specimens (129 of ASC-US, 82 of LSIL, and 89 of ASC-H) with positive HR-HPV DNA was detected by a two-probe dual-color FISH panel, targeting hTERC and the centromeric region of chromosome 3 (CSP3). Using >2 signals for hTERC together with ≥2 signals for CSP3 to define abnormal nucleus, and the cutoff value was set at 6.5 per random 200 nuclei displayed increased hTERC signals and/or tumor ploidy. Statistical analyses were based on histologic findings of colposcopy biopsies, allowing CIN2 or worse (CIN2+) as the positive criterion.
The FISH results were systematically analyzed among groups, based on histologic diagnosis, cytologic finding, HR-HPV viral load, and age status. hTERC presented good consistency with histology, and had satisfactory sensitivity, specificity, and accuracy among different groups, with less difference intergroup. The individual hTERC positive nuclei ratio was generally increased with severity of the cervical lesions.
hTERC could be a stable predictor in assuring the risk of high-grade CIN in women with mild cytologic abnormality and positive HR-HPV, and the individual positive nuclei ratio of it might be helpful in identifying morbid grade for cervical lesions.

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    • "Other factors may also contribute to the development of cervical cancer [5]. Studies have found that during the transforming process from atypical anomalies to cancer, almost all cervical epithelial cells showed abnormal hTERC amplification [6,8,17,18]. Human chromosome telomerase comprises telomerase mRNA (hTERC), telomerase reverse transcriptase (hTERT) and telomerase-binding protein (hTP1). "
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    ABSTRACT: Background Currently the routine non-invasive screening methods for cervical intraepithelial neoplasia (CIN) and cervical cancer are Thinprep cytology test (TCT) and human papillomavirus testing. However, both methods are limited by the high false positive and false negative rates and lack of association with patients’ prognosis, especially for the early detection of pro-malignant CIN. The aim of the study was to investigate the role of genomic amplification of human telomerase gene (hTERC) in the diagnosis and prognosis of CIN. Methods The study group consisted of specimens of exfoliated cervical cells from 151 patients, including 27 with CIN I, 54 with CIN II/III, 17 with carcinoma in situ, and 28 with invasive squamous carcinoma, as well as 25 patients who were at 2-year follow-up after either Loop Electrosurgical Excision treatment (n = 11) or radical surgery (n = 14). hTERC amplification was detected by dual-color interphase fluorescence in situ hybridization (FISH), and the results were compared with TCT and histologic examination. The final diagnosis was determined by the pathological examination. The control group consisted of specimens of exfoliated cervical cells from 40 normal women. Results The percentage of cervical exfoliated cells with positive hTERC amplification and incidence rates of hTERC amplification were 9.2% ± 4.6% and 44.4% (12/27) respectively in patients with CIN I; 16.0% ± 14.4% and 85.1% (46/54) in patients with CIN II/III; 19.7% ± 13.3% and 88.3% (15 /17) in patients with carcinoma in situ; 47.0% ± 25.2% and 100% (28/28)in patients with invasive squamous carcinoma. There was statistically significant difference between the control and study group (P <0.01), and between the patients with various diseases within the study group (P <0.05). Conclusion The detection of genomic amplification of hTERC using FISH is a non-invasive and effective approach for CIN.
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    ABSTRACT: We examined the diagnostic performance of fluorescence in situ hybridization (FISH) tests on cervical cytology for precancerous lesions or cancer on cervical histology. A search was conducted in MEDLINE, the Cochrane Central Register of Controlled Trials, and Scopus through September 3, 2013. Eleven studies examined FISH tests for telomerase RNA component gene (TERC), myelocytomatosis oncogene (MYC), or human papillomavirus (HPV) type 16 or 18 in samples exhibiting atypical squamous cells of unknown significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). None examined HPV-positive, cytologically normal samples. We extracted data on the sensitivity and specificity for high-grade cervical intraepithelial neoplasia (CIN 2+ or CIN 3+). Fluorescence in situ hybridization test probes and thresholds varied across studies. Included populations were convenience samples. Only 1 study testing for TERC specified HPV status. In meta-analysis, FISH for TERC in LSIL (9 studies, 1,082 cases) had a summary sensitivity of 0.76 (95% confidence interval = 0.63-0.85) and a summary specificity of 0.78 (95% confidence interval = 0.57-0.91) for CIN 2+. Fluorescence in situ hybridization for TERC in ASC-US (3 studies, 839 cases) showed sensitivities ranging from 0.75 to 1.00 and specificities from 0.87 to 0.93 for CIN 2+. For CIN 3+, sensitivity and specificity appeared similar, although a small number of studies preclude firm conclusions. For FISH tests for HPV, we found only few studies with small sample sizes. The evidence on FISH testing is limited given the small number of studies for each cytology subgroup and the lack of studies in well-defined screening contexts stratifying participants by HPV status.
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