Gain of human telomerase RNA gene is associated with progression of cervical intraepithelial neoplas

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Background The 3q26 chromosome region,where the human telomerase RNA gene (hTERC) is located,is a biomarker for cervical cancer and precancerous lesions.The aim of this study was to confirm the value of measuring hTERC gene gain in predicting the progression of cervical intraepithelial neoplasia grade Ⅰ or Ⅱ (CIN-Ⅰ and -Ⅱ,respectively) to CIN-Ⅲ and cervical cancer.Methods Liquid-based cytological samples from 54 patients with CIN-Ⅰ or CIN-Ⅱ lesions were enrolled in this study.Follow-up was performed with colposcopy and biopsy within 24 months after the diagnosis of CIN-Ⅰ or CIN-Ⅱ.Copy numbers of the hTERC gene were measured by fluorescence in situ hybridization with a dual-color probe mix containing the hTERC gene probe (labeled red) and the control,the chromosome 3 centromere-specific probe (labeled green).Results All patients whose lesions progressed from CIN-Ⅰ or CIN-Ⅱ to CIN-Ⅲ displayed a gain of the hTERC gene,whereas patients where the hTERC gene was not amplified did not subsequently progress to CIN-Ⅲ or cervical cancer.The signal ratio pattem per cell was recorded as N∶N (green∶ red).The numbers of cells with the signal ratio pattern of 4∶4or N∶≥5 in patients whose lesions progressed to CIN-Ⅲ were significantly higher than those whose lesions did not progress.Significantly,none of the patients with a 4∶4 signal ratio pattern regressed spontaneously.Conclusions In conclusion,measurement of hTERC gene gain in CIN-Ⅰ or CIN-Ⅱ patients using liquid-based cytological samples could be a useful biomarker to predict the progression of such cervical lesions.In addition,a 4∶4 or N∶≥5 signal ratio pattern may indicate the unlikeness of spontaneous regression of CIN-Ⅰ or CIN-Ⅱ lesions.
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