荧光原位杂交技术检测宫颈上皮内瘤变及宫颈癌中TERC基因的扩增及临床意义

目的:应用荧光原位杂交(FISH)技术检测宫颈上皮内瘤变(CIN)及宫颈癌中TERC基因的扩增,探讨其在宫颈病变筛查中的意义.方法:筛选门诊就诊宫颈疾病患者宫颈脱落细胞标本120例,其中液基细胞学检查正常者20例,病理学检查CIN Ⅰ、CINⅡ、CINⅢ及宫颈癌各25例.采用双色间期FISH技术检测宫颈脱落细胞TERC基因扩增,以正常标本的检测结果建立阈值.结果:①CIN Ⅰ、CINⅡ、CINⅢ及宫颈癌中每例的异常细胞百分率均大于阈值(P<0.05),异常细胞百分率随病理学分级病变严重程度增高而增高(P<0.01).②2:3、2:4、2:5和4:4以上类型在CIN Ⅰ、CINⅡ、CINⅢ及宫颈癌所占百分率比较,差异有高度统计学意义(均P<0.01),其中宫颈癌与CIN Ⅰ比较,2:3类型所占比例明显下降(P<0.001),2:4、2:5和4:4以上类型所占比例明显升高(JP<0.001).③不同细胞学分级中,异常细胞百分率随其病变严重程度增高而增高(P<0.01),2:3、2:5和4:4以上类型在ASCUS、LSIL和HSIL中的百分率差异有高度统计学意义(均P<0.01),其中HSIL与ASCUS比较,2:3类型所占比例明显下降(P<0.01),2:5和4:4类型所占比例明显升高(P<0.01).④在低级别及高级别CIN中,细胞学LSIL及HSIL检出率分别为10例(40.00%,10/25)及31例(62.00%,31/50),FISH技术检测出低级别与高级别CIN的敏感度均明显高于细胞学检查(P<0.05).结论:CIN Ⅰ、CINⅡ、CINⅢ及宫颈癌均有TERC基因扩增,其拷贝数随病理学及细胞学分级严重程度增加而增加.应用FISH技术检测宫颈脱落细胞TERC基因扩增对宫颈病变筛查及对病变进展预测具有一定价值.

Detection of Telomerase RNA Component Gene Amplification in Cervical Intraepithelial Neoplasia and Cervical Cancer with Fluorescence in Situ Hybridization and Its Clinical Significance

Objective:To investigate the amplification of the telomerase RNA component (TERC) gene in cervical cancer and cervical intraepithelial neoplasia (CIN) using dual-color interphase fluorescence in situ hybridization (FISH) and its significance in screening of cervical lesion. Methods:Cervical cast-off cell specimens were screened from 120 outpatients with cervical lesion, including normal cell from liquid based cytology (20 cases), CIN Ⅰ , Ⅱ , Ⅲ and cervical cancer cell from liquid based cytology (each of 25 cases). The amplification of TERC gene in cervical cast-off cells was detected by dual-color interphase FISH. The results of normal samples were used to set up the threshold. Results:①The percentages of abnormal cells in CIN Ⅰ , Ⅱ , Ⅲ and cervical cancer were significantly higher than threshold value ( P<0.05), and the percentage of abnormal cells was increased with the serious degree of pathological grade (P<0.01) ; ②The percentagesof 2:3,2:4,2:5 and great than or equal to 4:4 types in CIN Ⅰ , Ⅱ , Ⅲ and cervical cancer were significantdifferences (all P<0.01). The percentages of 2:4,2:5 and great than or equal to 4:4 types in cervical cancer were significant higher than that in CIN Ⅰ (P<0.001) while the percentage of 2:3 type was significant lower than that in it (P<0.001);③The percentage of abnormal cells was increased with the serious degree of cytological grade (P<0.01) in different cytological grades. The percentages of 2:3,2:5 and great than or equal to 4:4 types in atypical squamous cell of undetermined significance (ASCUS), low-grade squamous intraepithe-lial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) were significant differences (all P <0.01), and the percentages of 2:5 and great than or equal to 4:4 types in HSIL were significant higher than that in ASCUS( P <0.01) while the percentage of 2:3 type was significant lower than that in it ( P <0.01);④The detection rates of LSIL and HSIL with cytological examination in low grade and high grade CIN were 40% (10/25) and 62% (31/50) respectively, which were significant lower than the detection rates of FISH which was 100%(P<0.05).Conclusions:There is an abnormal amplification of TERC gene in CIN Ⅰ , Ⅱ , Ⅲ and cervical cancer, and its copy numbers are increased with the serious degree of pathological and cytological grades. Detection of amplification of TERC gene in cervical cast-off cells with FISH has a certain value for screening cervival lesion and prediction of lesion progression.