FISH检测宫颈脱落细胞中hTERC基因扩增的临床意义

Clinical significance of genetic amplication of the human telomerase gene in cytologic specimens of cervices detected by FISH

目的探讨宫颈上皮内瘤变（CIN）、宫颈癌患者hTERC基因扩增的临床意义。方法收集2008年2月-2009年2月新疆医科大学附属肿瘤医院120宫颈脱落细胞标本,按细胞学分组分为正常细胞组20例,无明确诊断意义的不典型鳞状细胞（ASCUS）组15例,低度鳞状上皮细胞内病变（LSIL）组25例,高度鳞状上皮细胞内病变（HSIL）20例,鳞状细胞癌（SCC）组40例;按组织学分组正常细胞学妇女20例,CIN患者60例,宫颈鳞状细胞癌（SCC）患者40例,荧光原位杂交（FISH）方法检测宫颈脱落细胞hTERC基因扩增情况。结果（1）在正常细胞组、ASCUS组、LSIL组、HSIL组和SCC组患者宫颈脱落细胞中hTERC基因扩增的阳性率分别是0%、33.3%、52.0%、80.0%和100%;正常细胞、ASCUS、LSIL、HSIL和SCC比较,差异有统计学意义（P〈0.05）;通过调整检验水准（α=0.005）后,进行组间两两比较,随细胞学病变程度增加,hTERC基因扩增的阳性率增加。（2）在CINⅠ、CINⅡ/Ⅲ和SCC患者宫颈脱落细胞中hTERC基因的扩增的阳性率分别是30%、67.5%和92.5%;CINⅠ、CINⅡ/Ⅲ、SCC组比较,hTERC基因扩增的阳性率差异有统计学意义（P〈0.01）,其中,CINⅠ与CINⅡ/Ⅲ、CINⅠ与SCC、CINⅡ/Ⅲ与SCC比较差异有统计学意义（P〈0.05）,其中SCC组hTERC基因拷贝数也明显增加。（3）.维、汉族CIN患者hTERC基因的扩增阳性率差异无统计学意义（P〉0.05）。结论hTERC基因在CIN和SCC中异常扩增,且随病变程度增加扩增阳性率增加,可作为宫颈病变进展的生物学监测指标;hTERC扩增在维、汉族CIN患者中无明显差异性。

Objective To evaluate the significance of amplification of the human telomerase component（hTERC） in the cytologic specimens of cervices.Methods The fluorescence signal of cytologic samples of cervices were detected by using interphase fluorescence in situ hybridization（FISH） in chromosome enumeration double-color DNA probes TERC.According to histologic biopsy,120 Pap smears were divided into normal（n=20）,cervical intraepithelial neoplasia（CIN,n=60）,squamous carcinomas of the cervices（SCC,n=40）.Results None normal samples revealed copy number increases of 3q,while 33.3% of theASCUS,52.0% of the LSIL,80.0% of the HSIL and100% of the squamous cervical cancer showed extra copies of 3q.TERC copy numbers in HSIL and SCC were significantly higher than in normal samples,ASCUS samples and LSIL samples.The percentage of multiple 3q signals increased with the severity of the cytology（P〈0.05）.None normal samples revealed copy number increases of 3q,while 30% of the CINⅠ,67.5% of the CINⅡ/Ⅲ lesions and 92.5% of the squamous cervical cancer showed extra copies of 3q.TERC 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）.Conclusion The increase of hTERC expression in the squamous cervical cancer and CIN suggests that 3q copy numbers are associated with the severity of cytologic and histologic findings.Therefore,application of the probe set may provide an objective genetic test for the assessment of cells in Pap smears and serves as a screening test marker for HSIL or CINⅡ/Ⅲ which may help to determine the progressive potential of individual lesions.