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目的探讨应用FISH技术检测人类染色体端粒酶(hTERC)基因异常扩增在子宫颈病变的临床意义。方法选择经过液基细胞学(TCT)检查的130例患者为研究对象,用荧光原位杂交(FISH)方法检测脱落细胞hTERC基因异常扩增情况,与病理结果金标准相比对。结果130例患者中正常细胞学妇女20例,病理检查炎症26例,C IN1患者34例,C IN2/3患者34例,鳞状细胞癌(SCC)患者16例,FISH检测hTERC基因异常扩增阳性率在炎症组是3.8%、C IN1组23.5%、C IN2/3组82.4%和SCC组100%,炎症组和C IN1组与C IN2/3组和SCC组比较,hTERC基因扩增阳性率差异有显著统计学意义(P<0.005)。随着病变程度增加,hTERC基因异常扩增阳性率增加。hTERC基因检测高级别病变(C IN2/3、鳞状细胞癌)的敏感度、特异度分别是88.0%、88.8%。C IN组hTERC基因平均拷贝数为2.18,SCC组平均拷贝数为3.05,SCC组hTERC基因拷贝数比C IN组明显增加(P<0.01),FISH检测结果显示,杂交信号hTERC基因高拷贝型比例在炎症组6.1%,C IN1组17.0%,C IN2/3组33.8%,SCC组47.7%,呈上升趋势(P<0.05)。宫颈病变向高级别进展组(n=7)与病变维持低级别或低级别转归组(n=12)的hTERC基因异常扩增阳性比分别为5/7和0/12,两组有明显差异(P<0.01)。平均拷贝数分别为2.19和2.04,两组有明显差异(P<0.05)。结论hTERC基因的异常扩增随宫颈病变级别增高而增加,并对宫颈早期病变进展有预测意义。应用FISH技术检测hTERC基因的异常扩增可作为监测宫颈病变进展的生物遗传学指标,协助TCT和高危HPV DNA检测诊断高级别C IN和鳞状细胞癌。
Objective To investigate the clinical significance of using FISH to detect the abnormal amplification of human telomerase (hTERC) gene in cervical lesions. Methods One hundred and thirty patients who underwent liquid-based cytology (TCT) were enrolled in this study. Fluorescence in situ hybridization (FISH) was used to detect the abnormal amplification of hTERC gene in exfoliated cells, which was compared with the gold standard of pathological results. Results Of the 130 patients, 20 were normal cytology, 26 were pathologically examined, 34 were C IN1, 34 were C IN2 / 3, 16 were squamous cell carcinoma (SCC), and abnormal amplification of hTERC was detected by FISH The positive rates were 3.8% in the inflammation group, 23.5% in the C IN1 group, 82.4% in the C IN2 / 3 group and 100% in the SCC group. The hTERC gene amplification was positive in the inflammation group and the CIN1 group as compared with the CIN2 / 3 group and the SCC group The difference was statistically significant (P <0.005). As the degree of lesion increases, the positive rate of abnormal amplification of hTERC gene increases. The sensitivity and specificity of hTERC gene in detecting high-grade lesions (CIN2 / 3, squamous cell carcinoma) were 88.0% and 88.8%, respectively. The average copy number of hTERC gene was 2.18 in CIN group and 3.05 in SCC group, and the copy number of hTERC gene in SCC group was significantly higher than that in CIN group (P <0.01). The FISH results showed that the high copy number of hybridization signal hTERC gene In inflammatory group 6.1%, C IN1 group 17.0%, C IN2 / 3 group 33.8%, SCC group 47.7%, an upward trend (P <0.05). The positive rates of abnormal amplification of hTERC gene in cervical lesions to high-grade progression group (n = 7) and lesion maintenance low-grade or low-grade outcome group (n = 12) were 5/7 and 0/12, respectively Difference (P <0.01). The average copy number was 2.19 and 2.04, respectively, with significant differences between the two groups (P <0.05). Conclusion The abnormal amplification of hTERC gene increases with the increase of cervical lesions and has a predictive value for the progression of early cervical lesions. Detecting the abnormal amplification of hTERC gene by FISH can be used as a biogenetic indicator to monitor the progression of cervical lesions, and help TCT and high-risk HPV DNA detection in the diagnosis of high-grade C IN and squamous cell carcinoma.