p16联合免疫组化标志物在妊娠期持续高级别宫颈鳞状上皮内病变中的诊断价值  

The value of p16 combined with cell morphology markers in accurate diagnosis of persistent high-grade cervical squamous intraepithelial lesions during pregnancy

作　　者：刘艳娇 李淑红[1] 白利颖[1] 曹冬焱[2] 杨佳欣[2] 沈铿[2] 孙恒子 Liu Yanjiao;Li Shuhong;Bai Liying(Department of Obstetrics & Gynecology,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100020)

机构地区：[1]首都医科大学附属北京朝阳医院妇产科,北京100020 [2]中国医学科学院北京协和医院妇产科,北京100730

出　　处：《现代妇产科进展》2022年第4期246-250,共5页Progress in Obstetrics and Gynecology

基　　金：中国医学科学院医学与健康科技创新工程(CIFMS-2017-I2M-1-002)。

摘　　要：目的检测妊娠期宫颈鳞状上皮内病变中p16、Ki-67、SMAD3、YAP1及RELA的表达,以期为妊娠期HSIL患者提供更精准的临床诊疗方案。方法收集首都医科大学附属北京朝阳医院及中国医学科学院北京协和医院2019年1月至2020年1月收治的122例妊娠期子宫颈癌筛查结果异常并转诊阴道镜宫颈多点活检患者。在患者妊娠期阴道镜活检病理中评估p16、Ki-67、SMAD3、YAP1、RELA蛋白表达水平,结合患者病理结果及转归进行相关性分析。结果患者中位年龄为33岁(21~42岁)。产前TCT结果ASCUS合并高危HPV阳性患者28例,LSIL患者44例,ASC-H患者8例,HSIL患者42例。阴道镜活检病理为组织学LSIL及以下病变者60例,组织学HSIL病变者62例。免疫组化结果显示,p16、Ki-67、SMAD3、YAP1、RELA蛋白在组织学HSIL病变中的表达明显高于在组织学LSIL及以下病变。产后6~12周内共109例患者再次行联合筛查,其中86例患者再次行阴道镜检查活检,病理结果为组织学HSIL病变为45例,妊娠期HSIL自然消退率为47.5%。联合免疫组化分析显示,p16+联合RELA+和(或)YAP1+较单独p16+在诊断妊娠期持续组织学HSIL中具有相当的敏感度(66.7%vs 68.9%,P=0.822)及更高的特异度(84.4%vs 65.6%,P=0.014),且具有最大ROC曲线下面积(AUC为0.747,95%CI=0.650~0.845)。结论妊娠期HSIL患者约半数以上可自然消退,p16联合RELA和(或)YAP1高表达对妊娠期持续组织学HSIL有较高的诊断价值。Objective:To detect the expressions of p16,Ki-67,SMAD3,YAP1 and RELA in cervical squamous intraepithelial lesions,so as to provide accurate clinical diagnosis and treatment strategy for HSIL patients during pregnancy.Methods:A collection of patients with pregnancy recommended for colposcopy biopsy admitted to Beijing Chaoyang Hospital of Capital Medical University and PUMCH from January 2019 to January 2020.The expressions of p16,Ki-67,SMAD3,YAP1,RELA were evaluated in enrolled patients.The correlation analysis was carried out based on the pathological results and outcomes of the patients.Results:The median age of the patients was 33(21~42).The cohort including 28 cases of ASCUS combined high-risk HPV-positive patients,44 cases of LSIL,8 cases of ASC-H,42 cases of HSIL.Biopsy showed a total of 60 cases with histological LSIL and below,and 62 cases with histological HSIL.The IHC results showed that the expressions of p16,Ki-67,SMAD3,YAP1 and RELA were significantly higher in histological HSIL than LSIL and below.A total of 109 patients underwent co-testing within 6~12 weeks postpartum.86 of 109 patients reviewed colposcopy biopsy.The pathological results showed that 45 cases were histological HSIL.Moreover,the spontaneous regression rate of HSIL during pregnancy was 47.5%.Combined analysis showed that p16+combined with RELA+and/or YAP1+has considerable sensitivity(66.7%vs 68.9%,P=0.822)and a higher specificity(84.4%vs 65.6%,P=0.014)than p16+alone in diagnosing persistent HSIL during pregnancy.The p16+combined with RELA+and/or YAP1+also has the largest AUC(0.747,95%CI=0.650~0.845).Conclusion:About half of HSIL patients during pregnancy can resolve spontaneously.The high expression of p16 combined with RELA and/or YAP1 has a higher diagnostic value for persistent HSIL during pregnancy,which provides a basis for exploring the screening and triage strategy for cervical cancer in pregnancy.

关 键 词：妊娠期 宫颈病变 P16 YAP1 RELA 

分 类 号：R737.33[医药卫生—肿瘤]