应用荧光原位杂交技术在组织标本中检测宫颈上皮病变的端粒酶RNA基因扩增  

Detection of TERC gene amplification by fluorescence in-situ hybridization in cervical intraepitheliallesions

作　　者：袁艳龙[1] 何春年[1] 徐明堂[1] 徐翠清[2] 孙玉宁[1] 赵焕芬[1] 陈琛[1] 

机构地区：[1]河北省人民医院病理科,石家庄950051 [2]河北省人民医院妇产科,石家庄050051

出　　处：《中华病理学杂志》2011年第3期182-186,共5页Chinese Journal of Pathology

基　　金：河北省科技支撑计划项目（08276101D-101）

摘　　要：目的 用荧光原位杂交（FISH）技术检测端粒酶RNA基因（TERC）在宫颈上皮内瘤变（CIN）和宫颈鳞状细胞癌（scc）组织中的扩增，探讨其用于SCC筛查及CIN诊断的可行性及实际意义。方法选取手术切除及活检的子宫颈组织标本196例，有效样本150例，采用FISH技术在石蜡包埋组织芯片上检测TERC基因的扩增情况。结果150例组织芯片样本中，正常宫颈鳞状上皮24例，CIN78例（CINI级25例，Ⅱ级21例，Ⅲ级32例），SCC48例。正常宫颈鳞状上皮组织中TERC基因无扩增，从CINI级到SCC组织中，TERC基因的扩增率依次为8．0％（2／25）、47．6％（10／21）、71．9％（23／32）和87．5％（42／48），差异有统计学意义（P〈0．05）。组问两两比较：正常宫颈鳞状上皮与CINⅡ级、Ⅲ级、SCC组，组间比较差异均有统计学意义（P〈0．05）；CINⅠ级与C1NⅡ级、Ⅲ级及SCC组组问比较，差异有统计学意义（P〈0．05）；CINⅡ级组与SCC组相比，差异有统计学意义（P〈0．05）。正常宫颈鳞状上皮与CINⅠ级组、CINⅡ级与Ⅲ级组、CINⅢ级与SCC组，组问差异均无统计学意义（P〉0．05）。高度癌前病变（CINⅡ～Ⅲ级）与低度癌前病变（CINⅠ级）的TERC基因扩增结果：25例CINⅠ级病变中，2例扩增，23例不扩增；53例CINⅡ—Ⅲ级病变中，33例扩增，20例不扩增。经公式计算，敏感性为62．3％、特异性为92．0％、准确度为71．8％、阳性预测值为94．3％、阴性预测值为53．5％。结论在石蜡包埋CIN及SCC组织切片上应用FISH技术进行TERC基因检测，方法可行，结果可靠；可作为辅助CINⅡ级的诊断；TERC基因扩增可以预测CIN发展为癌的风险，具有一定的实用价值。Objective To explore the feasibility and practical value of fluorescence in situ hybridization （FISH） detection of TERC gene amplification in cervical intraepithelial lesions （CIN） and squamous cell carcinoma （ SCC ） . Methods Tissue microarray was constructed to cover 150 cases of various cervical conditions, including 24 cases of normal cervical mucosa, 78 cases of CINs （CINⅠ, 25 cases; CINⅡ , 21 cases and CIN Ⅲ, 32 cases） and 48 cases of SCC. FISH was used to detect TERC gene amplification. Results TERC gene amplification was detected in 8% （2/25） CIN Ⅰ, 47.6% （ 10/21 ） CIN Ⅱ, 71.9% （23/32） CIN Ⅲ and 87.5% （42/48） SCC. There were significant differences among these groups （P 〈 0.05） . The amplification rates of TERC gene in SCC, CIN m and CIN Ⅱ were significantly higher than those of normal cervical epithelium and CIN Ⅰ （ P 〈 0. 05 ）. Significant differences were also observed among CIN Ⅰ and CIN Ⅱ, CIN Ⅲ and SCC （P 〈 0. 05 ） , and between CIN Ⅱ and SCC （P 〈 0. 05 ）. There were no significant differences between normal cervical epithelium and CIN Ⅰ , CIN Ⅱ and CIN m, and between CIN Ⅲ and SCC （P 〉 0. 05）. FISH detection of amplification of TERC gene in CIN I and CIN Ⅱ-Ⅲ demonstrated the following statistics： sensitivity of 62. 3%, specificity of 92. 0%,accuracy of 71.8%, positive and negative predictive values of 94.3% and 53.5%, respectively. Conclusions FISH detection is a reliable method in detecting TERC gene amplification using paraffin tissue sections. When histological evaluation becomes difficult, TERC amplification detectable by FISH may offer a diagnostic distinction of CIN Ⅰ from CIN Ⅱ. Moreover, TERC amplification may be used as a biomarker in predicting CIN orogression to invasive cancer.

关 键 词：宫颈上皮内瘤样病变 肿瘤 鳞状细胞 原位杂交 荧光 基因扩增 端粒 末端转移酶 

分 类 号：R737.33[医药卫生—肿瘤]