摘要
目的探讨TERC基因作为宫颈病变筛查指标的临床意义。方法选取在北京大学人民医院和北京大学深圳医院妇科门诊进行宫颈病变筛查的715例患者为研究对象，对其宫颈脱落细胞行液基细胞学检查，并行第2代杂交捕获试验（HC—Ⅱ）检测高危型人乳头状瘤病毒（HPV），必要时行阴道镜活检及病理检查。荧光原位杂交（FISH）技术检测细胞内TERC基因的异常扩增情况。以病理检查结果为“金标准”，将TERC基因异常扩增结果与液基细胞学检查和高危型HPV检测结果进行比较。结果在宫颈液基细胞学检查结果为正常、未明确诊断意义的不典型鳞状上皮细胞（ASCUS）、不除外高度病变的不典型鳞状上皮细胞（ASC—H）、低度鳞状上皮内病变（LSIL）、高度鳞状上皮内病变（HSIL）和不典型腺细胞（AGC）中，TERC基因异常扩增率分别为5．8％、22．2％、30．8％、27．8％、86．4％和1／1，正常、ASCUS、ASC—H和LSIL者均明显低于HSIL者（P〈0．01）。在病理检查结果为宫颈上皮内瘤变（CIN）Ⅰ、CINⅡ～Ⅲ和浸润癌中，TERC基因异常扩增率分别为9．3％、77．8％和96．7％，CINⅠ明显低于后两者（P〈0．01）。HPV检测结果为阳性患者的TERC基因扩增阳性率明显高于HPV阴性者（分别为33．5％和5．2％，P〈0．01）。TERC基因异常扩增诊断CINⅡ及以上病变的敏感度为81．88％，明显高于细胞学检查的36．96％（P〈0．01）；其特异度（93．32％）明显高于HPV检测的33．93％（P〈0．01）；阳性预测值（81．29％）与细胞学检查（86．44％）相似（P〉0．05）；而阴性预测值（93．56％）低于HPV检测（97．06％，P〈0．05）。结论随着宫颈病变程度的加重，TERC基因异常扩增率增加，且其扩增与HPV感染有关。应用FISH技术检测TERC基因异常扩增作为分子遗传学指标，可以辅助细胞学检查和HPV检测，协助筛出CINⅡ及以上的高度病变和宫颈癌。
Objective To investigate the significance of genomic amplification of the telomerase RNA component （ TERC ） gene to serve as a genetic biomarkcr in the screening of cervical lesions. Methods A total of 715 cases were recruited, with liquid-based cytology diagnosis as normal （n = 347）, atypical squamous cells of undetermined significance （ASCUS, n = 180） , atypical squamous cells cannot exclude a high-grade lesion （ASC-H, n = 13）, low-grade squamous intraepithelial lesions （LSIL, n = 115 ）, high- grade squamous intraepithelial lesions （ HSIL, n = 59） and atypical glandular cells （ AGC, n = 1 ）. The remaining cervical cells in the cytological preserving fluid were analyzed using a two-color fluorescence in situ hybridization （FISH） probe targeted to chromosome 3q26 containing TERC gene. The TERC gene findings were compared to the cytological and histological detected results, as well as high-risk human papillomavirus （HPV） detected results. Results Genomic amplification of TERC gene was found in 5.8% of normal specimens, 22. 2% of ASCUS, 30. 8% of ASC-H, 27.8% of LSIL, 86.4% of HSIL and 1/1 of AGC. The positive rate was significantly lower in normal, ASCUS, ASC-H and LSIL compared with HSIL （ all P 〈 0. 01）. Significantly more cells with genomic amplification of TERC gene were found in cervical intraepithelial lesion （CIN） Ⅱ-Ⅲ than CIN Ⅰ （77.8% vs. 9.3% ）, as well as invasive cervical cancer （96. 7% vs. 9. 3% ）, both P 〈 0. 01. The rate of TERC gene amplification was higher in HPV positive patients （ 33.5% ） than in HPV negative patients （ 5.2%, P 〈 0. 01 ）. The sensitivity of TERC gene amplification was significantly higher than that of cytological screening （81.88% vs. 36. 96%, P 〈 0. 01 ） in the differentiation of CIN Ⅱ or higher and CIN Ⅰ or lower diseases, its specificity was higher than highrisk HPV test （93.32% vs. 33.93%, P 〈0. 01 ） and positive prediction value （81.29%） was similar with cytological method （86. 44%, P 〉0.05） ; but its negative prediction value （93.56%） was lower than HPV test （97. 06%, P 〈 0. 05 ）. Conclusions The positive rates of TERC gene amplification increased as cervical diseases worsened. TERC gene amplification is related to HPV infection. The gain of chromosome 3q26 in cytological specimens is an effective molecular genetic biomarker in screening of CIN Ⅱ or higher and invasive cervical cancer.
出处
《中华妇产科杂志》
CAS
CSCD
北大核心
2009年第12期883-886,共4页
Chinese Journal of Obstetrics and Gynecology
基金
基金项口：卫生部科研基金（WKJ2007-3-001）
关键词
宫颈肿瘤
宫颈上皮内瘤样病变
乳头状瘤病毒
人
端粒
末端转移酶
原位杂交
荧光
Cervix neoplasms
Cervical intraepithelial neoplasia
Papillomavirus, human
Telomerase
In situ hybridization, fluorescence
