不同检测标志物在宫颈腺癌中的诊断和预后预测价值评估  

Assessment of the diagnostic value and prognosis of different detection markers in endocervical adenocarcinoma

作　　者：张倡宁 刘潇阳 李青[3] 宋益哲 刘彬 阴建[5] 杨敬红 钟理[1] 孙力 张询[5] 陈汶 Zhang Changning;Liu Xiaoyang;Li Qing;Song Yizhe;Liu Bin;Yin Jian;Yang Jinghong;Zhong Li;Sun Li;Zhang Xun;Chen Wen(School of Life Science,Hebei University,Baoding 071002,China;Department of Pathology,Peking University,People′Hospital,Beijing 100044,China;Department of Pathology,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100021,China;Department of Cancer Epidemiology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100021,China;School of Population Medicine and Public Health,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China;Department of Gynecology,Mianyang Maternity&Child Healthcare Hospital,Mianyang 621000,China;National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Shenzhen 518116,China)

机构地区：[1]河北大学生命科学学院,保定071002 [2]北京大学人民医院病理科,北京100044 [3]首都医科大学附属北京朝阳医院病理科,北京100027 [4]国家癌症中心、国家肿瘤临床医学研究中心、中国医学科学院北京协和医学院肿瘤医院肿瘤流行病室,北京100021 [5]中国医学科学院北京协和医学院群医学及公共卫生学院,北京100730 [6]绵阳市妇幼保健院妇产科,绵阳621000 [7]国家癌症中心、国家肿瘤临床医学研究中心、中国医学科学院北京协和医学院肿瘤医院深圳医院妇科,深圳518116

出　　处：《中华肿瘤杂志》2023年第5期402-409,共8页Chinese Journal of Oncology

基　　金：深圳市医疗卫生三名工程项目(SZSM201812075);四川省科技计划应用基础研究项目(21YYJC3520)。

摘　　要：目的研究不同检测标志物在宫颈腺癌组织学类型中的诊断价值,及其对患者预后的预测价值。方法纳入2005—2010年中国医学科学院肿瘤医院宫颈腺癌患者54例,根据2018年国际宫颈腺癌分类标准将宫颈腺癌分为人乳头瘤病毒(HPV)相关性腺癌(HPVA)和非HPV相关性腺癌(NHPVA)。采用全组织切片聚合酶链反应(WTS-PCR)检测宫颈腺癌组织中的高危型人乳头瘤病毒(HR-HPV)DNA,E6/E7 mRNA原位杂交(ISH)技术检测HR-HPV E6/E7 mRNA。随机选取15例WTS-PCR检测阳性的组织样本进行激光显微切割聚合酶链反应(LCM-PCR),验证WTS-PCR和E6/E7 mRNA ISH两种检测方法的准确性。采用受试者工作特征(ROC)曲线分析标志物鉴别HPVA和NHPVA的效能。对宫颈腺癌患者预后影响因素进行单因素分析和多因素Cox比例风险模型回归分析。结果54例宫颈腺癌患者中,30例为HPVA,24例为NHPVA。HPVA患者的HR-HPV DNA阳性率为96.7%(29/30),HR-HPV E6/E7 mRNA阳性率为63.3%(19/30);NHPVA患者的HR-HPV DNA阳性率为33.3%(8/24),HR-HPV E6/E7 mRNA阳性率为0(0/24),差异均有统计学意义(均P<0.001)。LCM-PCR检测结果显示,5例患者腺上皮病变区域HR-HPV DNA阳性,余均阴性,与E6/E7 mRNA ISH检测结果一致性强(Kappa=0.842,P=0.001)。ROC曲线分析显示,HR-HPV DNA、HR-HPV E6/E7 mRNA和p16表达鉴别HPVA和NHPVA的AUC分别为0.817、0.817和0.692,灵敏度分别为96.7%、63.3%和80.0%,特异度分别为66.7%、100.0%和58.3%。HR-HPV DNA鉴别HPVA和NHPVA的AUC高于p16表达(P=0.044)。HR-HPV DNA(WTS-PCR检测)阳性与阴性患者的生存率差异无统计学意义(P=0.156),而HR-HPV E6/E7 mRNA阳性与阴性患者、p16表达阳性与阴性患者的生存率差异均有统计学意义(均P<0.05)。多因素Cox回归分析显示,国际妇产科联盟分期(HR=19.875,95%CI:1.526~258.833)和宫旁受累(HR=14.032,95%CI:1.281~153.761)是宫颈腺癌患者预后的独立影响因素。结论HPV E6/E7 mRNA更能反映宫颈腺癌组织中HPV的感染情�Objective To study the diagnostic value of different detection markers in histological categories of endocervical adenocarcinoma(ECA),and their assessment of patient prognosis.Methods A retrospective study of 54 patients with ECA in the Cancer Hospital,Chinese Academy of Medical Sciences from 2005-2010 were performed.The cases of ECA were classified into two categories,namely human papillomavirus-associated adenocarcinoma(HPVA)and non-human papillomavirus-associated adenocarcinoma(NHPVA),based on the 2018 international endocervical adenocarcinoma criteria and classification(IECC).To detect HR-HPV DNA and HR-HPV E6/E7 mRNA in all patients,we used whole tissue section PCR(WTS-PCR)and HPV E6/E7 mRNA in situ hybridization(ISH)techniques,respectively.Additionally,we performed Laser microdissection PCR(LCM-PCR)on 15 randomly selected HR-HPV DNA-positive cases to confirm the accuracy of the above two assays in identifying ECA lesions.Receiver operating characteristic(ROC)curves were used to analyze the efficacy of markers to identify HPVA and NHPVA.Univariate and multifactorial Cox proportional risk model regression analyses were performed for factors influencing ECA patients′prognoses.Results Of the 54 patients with ECA,30 were HPVA and 24 were NHPVA.A total of 96.7%(29/30)of HPVA patients were positive for HR-HPV DNA and 63.3%(19/30)for HR-HPV E6/E7 mRNA,and 33.3%(8/24)of NHPVA patients were positive for HR-HPV DNA and HR-HPV E6/E7 mRNA was not detected(0/24),and the differences were statistically significant(P<0.001).LCM-PCR showed that five patients were positive for HR-HPV DNA in the area of glandular epithelial lesions and others were negative,which was in good agreement with the E6/E7 mRNA ISH assay(Kappa=0.842,P=0.001).Analysis of the ROC results showed that the AUC of HR-HPV DNA,HR-HPV E6/E7 mRNA,and p16 to identify HPVA and NHPVA were 0.817,0.817,and 0.692,respectively,with sensitivities of 96.7%,63.3%,and 80.0%and specificities of 66.7%,100.0%,and 58.3%,respectively.HR-HPV DNA identified HPVA and NHPVA with

关 键 词：宫颈腺癌 人乳头瘤病毒 全组织切片聚合酶链反应 E6/E7 mRNA原位杂交 激光显微切割 预后 

分 类 号：R737.33[医药卫生—肿瘤]