Abstract
BackgroundHuman papillomavirus (HPV) infection plays an etiological role in the development of cervical dysplasia and cancer. Amplification of human telomerase gene (hTERC) and over expression of telomerase were found to be associated with cervical tumorigenesis. This study was performed to analyze genomic amplification of hTERC gene, telomerase activity in association with HPV infection in different stages of cervical intraepithelial neoplasia (CIN) and cervical cancer. We were studying the role of hTERC in the progression of uterine cervical dysplasia to invasive cancer, and proposed an adjunct method for cervical cancer screening.MethodsExfoliated cervical cells were collected from 114 patients with non neoplastic lesion (NNL, n=27), cervical intraepithelial neoplasia (CIN1, n=26, CIN2, n=16, CIN3, n=24) and cervical carcinoma (CA, n=21), and analyzed for amplification of hTERC with two-color fluorescence in situ hybridization (FISH) probe and HPV-DNA with Hybrid Capture 2.From these patients, 53 were taken biopsy to analyze telomerase activity by telomeric repeat amplification protocol (TRAP) and expression of human telomerase reverse transcriptase (hTERT), with immunohistochemistry (IHC). All biopsies were clinically confirmed by phathologists.ResultsAmplification of hTERC was significantly associated with the histologic diagnoses (p<0.05). The positive correlation was found between the level of hTERC amplification and histologic grading of dysplasia (CIN2/3 from CIN1 or normal, P=0.03). A profounding increase in the accumulation of HPV and hTERC positive cases was observed in the CIN3 subgroup compared with the CIN2 group, 25% versus 62.96%, respectively (p=0.007).ConclusionshTERC ampliffication can be detected with FISH technique on exfoliated cervical cells. Amplification of hTERC and HPV infection are associated with more progressive CIN3 and CA. The testing of hTERC amplification might be a supplementary to cytology screening and HPV test, especially high-risk patients.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1857134686755648.
Highlights
Genomic amplification of hTERC fluorescence in situ hybridization (FISH) analysis was performed on 114 cervical exfoliated specimens, and 11 of them were excluded because of the lack of hybridization signals or too few cells on slides
This analysis reveals that the average number of hTERC-positive cases increases with escalating levels of dysplasia
We found that telomerase activity was higher in CIN3/CA compared to control normal or CIN1/2(P=0.00); The levels of telomerase activity were 0.473±0.259 in normal group, 1.104±0.347 in CIN1, 1.350±0.347 in CIN2, 3.342±0.194 in CIN3, 4.318±0.274 log10[total product generated (TPG)] in CA
Summary
Cervical cancer (CC) is the second leading cause of cancer deaths in women, with more than 80% of these occurring in developing countries that have limited access to screening programs. It always takes about ten years to arise from precancerous lesion to invasive cervical cancer. For this reason, the effective screening of precursor lesion is of great importance, which makes cervical cancer preventable and curable. Human papillomavirus (HPV) infection plays an etiological role in the development of cervical dysplasia and cancer. This study was performed to analyze genomic amplification of hTERC gene, telomerase activity in association with HPV infection in different stages of cervical intraepithelial neoplasia (CIN) and cervical cancer. We were studying the role of hTERC in the progression of uterine cervical dysplasia to invasive cancer, and proposed an adjunct method for cervical cancer screening
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