免疫细胞化学p16/Ki-67双染色法检测对于细胞学诊断为ASCUS、LSIL和ASC-H患者分流的意义  

Significance of p16/Ki-67 double immunocytochemical staining in cervical cytology ASCUS, LSIL, and ASC-H

作　　者：吴忧[1] 赵健[1] 胡君[1] 吴向伟 朱丽荣[1] 

机构地区：[1]北京大学第一医院妇产科,100034

出　　处：《中华妇产科杂志》2017年第11期734-739,共6页Chinese Journal of Obstetrics and Gynecology

摘　　要：目的在细胞学诊断为未明确诊断意义的不典型鳞状上皮细胞（ASCUS）、低级别鳞状上皮内病变（LSIL）、不除外高度病变的不典型鳞状上皮细胞（ASC-H）的患者中，评价免疫细胞化学p16/细胞增殖相关核抗原（Ki-67）双染色法对其中高级别子宫颈病变[包括子宫颈上皮内瘤变（CIN）Ⅱ、CINⅢ]的筛查效能，并分析p16/Ki-67双染色法对于ASCUS、LSIL、ASC-H患者分流的意义。方法收集2015年10月—2016年3月在北京大学第一医院妇科门诊就诊的液基薄层细胞学检查（TCT）结果为ASCUS、LSIL、ASC-H的患者共251例，对其子宫颈脱落细胞分别行p16/Ki-67双染色法检测、高危型HPV（HR-HPV）检测[采用第2代杂交捕获技术（HC-Ⅱ）检测HR-HPV DNA]，并行阴道镜活检组织的病理检查，以组织学病理诊断为＂金标准＂，采用敏感度、特异度、阳性预测值、阴性预测值和受试者工作特征（ROC）曲线下面积比较p16/Ki-67双染色法和HR-HPV检测的筛查效能。结果（1）251例患者的子宫颈脱落细胞中，p16/Ki-67双染色的总阳性率为21.1%（53/251）。其中，细胞学诊断为ASCUS患者的子宫颈脱落细胞中p16/Ki-67双染色的阳性率为13.9%（15/108），LSIL患者为21.6%（22/102），ASC-H患者为39.0%（16/41），3者比较，差异有统计学意义（χ2=78.516，P〈0.05）；阴道镜活检后病理诊断为低级别子宫颈病变（包括正常子宫颈、CINⅠ）患者的子宫颈脱落细胞中p16/Ki-67双染色的阳性率为13.0%（28/215），高级别子宫颈病变患者为69.4%（25/36），两者比较，差异有统计学意义（χ2=7.932，P〈0.05）。（2）以阴道镜活检后的病理诊断为＂金标准＂，在细胞学诊断为ASCUS、LSIL、ASC-H的患者中，p16/Ki-67双染色法筛查高级别子宫颈病变的特异度（分别为89.8%、83.3%、88.9%）及阳性预测值（分别为33.3%、31.8%、81.3%）均明显高于HR-HPV检测（特异度分别�ObjectiveTo investigate the application value of p16/cell proliferation associated nuclear antigen （Ki-67） double-staining and human papillomavirus mRNA in the cytological screening.MethodsTwo hundred and fifty-one cases who suffered from atypical squamous cell of undetermined significance （ASCUS）, low-grade squamous intraepithelial lesion （LSIL）, atypical squamous cell-cannot exclude high-grade squamous intraepithelial lesion （ASC-H） in ThinPrep cytologic test （TCT） were collected in Peking University First Hospital between October 2015 and March 2016. And p16/Ki-67 double-staining and hybrid capture Ⅱ （HC-Ⅱ） detection were performed on the cervical cells. The result was compared with the pathological result of colposcope guided biopsy. All statistical analysis was completed by Stata 12.0 statistical software analysis. The results of diagnostic tests were described by using the sensitivity, specificity, positive predictive value,negative predictive value, and the area under the receiver operating characteristic （ROC） curve.Results（1） One hundred and eight cases of liquid based cytology diagnosis of ASCUS patients, the positive rate of p16/Ki-67 was 13.9% （15/108）, 102 cases of liquid based cytology diagnosis of LSIL patients, the positive rate of p16/Ki-67 was 21.6% （22/102）, 41 cases of liquid based cytology diagnosis of ASC-H patients, the positive rate of p16/Ki-67 was 39.0% （16/41）, compared amongthree groups, the difference was statistically significant （χ2=78.516, P〈0.05）; cervical exfoliated cells p16/Ki-67 expression rate was 13.0%（28/215） in cervical low-grade lesions [cervical intraepithelial neoplasia （CIN） Ⅰ], which was 69.4%（25/36） in high level lesions （CIN Ⅱ-Ⅲ）, the difference was statistically significant （χ2=7.932, P〈0.05）. （2） The specificity of p16/Ki-67 detection and diagnosis were higher than those of HC-Ⅱ in ASCUS, LSIL, and ASC-H （89.8% vs 71.4%, 83.3% vs 15.6%, 88.9% vs 40.7%; all P〈0.05）, mean

关 键 词：宫颈非典型鳞状细胞 宫颈肿瘤 宫颈上皮内瘤样病变 周期素依赖激酶抑制 剂p16 Ki-67抗原 免疫组织化学 细胞诊断学 

分 类 号：R737.33[医药卫生—肿瘤]