Evaluation Of Genomic Amplification Of The Human Telomerase RNA Component(hTERC) In The Screening Of Cervical Lesions

Objective:To investigate the genomic amplification of the human telomerase RNA component(hTERC) gene in cervical cytology and evaluate its role in screening of cervical lesions.To evaluate the prospect of fluorescence in situ hybridization (FISH) in screening of cervical lesions in future.Methods:A total of 130 cases were recruited before examination and treatment, with liquid-based cytology(LCT) diagnosis as negative for intraepithelial lesion or malignancy(NILM,n＝15),atypical squamous cells(ASC,n＝59),low-grade squamous intraepithelial lesions(LSIL,n＝24),high-grade squamous intraepithelial lesions(HSIL, n＝25),squamous cell carcinoma(SCC,n＝5),and adenocarcinoma(ADCA,n＝2). Following cytological examination,the slides were analyzed using a two-colour FISH probe targeted to chromosome 3q26 containing hTERC.The patients with abnormal LCT results were suggested for colposcopy to get the histologic results:inflammation (n＝21),cervical intraepithelial neoplasia(CIN)Ⅰ(n＝36),Ⅱ(n＝22),Ⅲ(n＝31),SCC (n＝12)and ADCA(n＝2).The hTERC findings were compared to the cytologic and histologic results,as well as high-risk human papilloma virus(HPV) results.Results:There are 2 green signals and 2 red signals in normal cells,if there are more than 2 red signals and no less than 2 green signals in one cell,we recognized it as a abnormal cell.There are 125 having results in the 130 samples.The achievement ratio is 96.3%0 The lost 5 samples with 1 normal and 4 ASC results of LCT were diagnosis as 3 inflammation and 2 CINⅠof histologic results.Significantly more cells with 3q26 gain were found in CINⅠthan in inflammation(29.41%vs 0%),as well as in CINⅡ(77.27%vs 0%),CINⅢ(83.87%vs 0%) and in SCC than in inflammation(100%vs 0%)(all P＜0.05).The significant difference was also found in CINⅡ,CINⅢand SCC than in CINⅠ(all P＜0.05).The abnormal hTERC signal type mostly was 2:3 in CINⅠ(69.79%);whereas in CINⅡ～Ⅲ,2:3,2:4 and 4:4 accouted for 36.34%,17.01%and 14.39%,respectively.The significant difference of 2:3 and 4:4 were found in CINⅡ～Ⅲthan in CINⅠ(all P＜0.05).The abnormal hTERC signal type 2:3,2:5 and 5:5 accouted for 18.98%,10.66%and 17.91%,respectively.The significant difference of 2:3 and 5:5 were found in SCC than in CINⅠand CINⅡ～Ⅲ(all P＜0.05).Genomic amplification of hTERC was found in 21.43%(3/14) of normal specimens,40.00%(22/55) of ASC,58.33%(14/24) of LSIL,84.00%(21/25)of HSIL and 100.00%(5/5) of SCC.The sensitivity of hTERC amplification was significantly higher than cytological screening(83.58%vs 41.79%,P＜0.05)),and its specification was higher than high-risk HPV test(82.76%vs 40%,P＜0.05)in diagnosis of high-grade cervical lesions.Conclusion:Testing the gain of chromosome 3q26 in cytological specimens using specific probe for hTERC is powerful to increase the sensitivity and specificity in screening of high-grade cervical lesion.The amplification patterns of 2:4,4:4 and5:5 may serve as potential prognosis makers.Amplification of FISH method can accurately detect the abnormal cells and be used as the screening method of hTERC gene.