FISH检测宫颈脱落细胞hTERC基因的表达及其临床意义

目的:探讨宫颈上皮内瘤变(CIN)患者人类染色体末端酶(hTERC)基因的表达和临床意义。方法:收集2006年10月至2007年6月北京大学人民医院妇科122例宫颈脱落细胞标本,其中CIN患者66例、宫颈鳞癌(SCC)患者20例、正常细胞学妇女36例,用荧光原位杂交(FISH)方法检测脱落细胞hTERC基因。结果:在CINⅠ、CINⅡ/Ⅲ和SCC患者宫颈脱落细胞中hTERC基因的表达率分别是16.13%、48.57%和90%,CINⅠ、CINⅡ/Ⅲ、SCC组与正常组比较,hTERC基因阳性率差异有显著统计学意义(P<0.001),其中,CINⅠ与CINⅡ/Ⅲ、CINⅠ与SCC比较,CINⅡ/Ⅲ与SCC比较差异有统计学意义(P<0.05)。随着病变程度增加,hTERC基因表达率增加。hTERC基因检测CINⅡ/Ⅲ的敏感度、特异度、阳性预测值和阴性预测值分别是48.57%、92.53%、77.27%和77.5%。CIN和SCC组hTERC基因拷贝数明显增加,其中CIN患者平均拷贝数为2.8,SCC组平均拷贝数为3.2,hTERC基因的表达水平与宫颈病变的程度关系密切。结论:hTERC基因在CIN和SCC中表达异常,且随病变程度增加阳性表达率增加,可作为宫颈癌前病变进展的生物遗传学监测指标。

Expression of the human telomerase gene in cytologic specimens of cervix

Objective：To evaluate the significance of dual-color interphase fluorescence in situ hybridization（FISH） of the human telomerase gene （hTERC） in the cytologic specimens of cervix. Methods：The fluorescence signal of cytologic samples of cervix were detected by using interphase FISH in chromosome enumeration double-color DNA probes TERC. According to histology biopsy, 122 Pap smears divided into normal （ n = 36 ） , cervical intraepithelial neoplasia （ CIN, n = 66）, squamous carcinomas of the cervix （ SCC, n = 20）. Results： None normal samples revealed copy number increases of 3q,while 16.13% of the CINI,48.57% of the CINⅡ/Ⅲ lesions and 90% of the squamous cervical cancer showed extra copies of 3q. TERC gene copy numbers in CINⅡ/Ⅲ were significantly higher than that in CINⅠ. The percentage of multiple 3q signals increased with the severity of the cytologic interpretation（P 〈 0. 05 ）. The sensitivity of our test for predicting progression from CINI to CINⅡ/Ⅲ was 48.57% and the specificity was 92.53%. We observed high proportions of nuclei with increased absolute copy numbers for TERC in CINⅡ/Ⅲ and SCC. The mean copy numbers were 2.8 and 3.2 respectively. Condusion： The increase of hTERC expression in the invasive SCC and CIN suggests that 3q copy numbers are associated with the severity of cytologic and histologic findings. Therefore, application of our probe set may provide an objective genetic test for the assessment of cells in Pap smears and serves as a screen-ing test marker for HSIL or CINⅡ/Ⅲ which may help to determine the progressive potential of individual lesions.