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. (Chinese)

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 higher AUC than p16 (P=0.044). The difference in survival rates between HR-HPV DNA (WTS-PCR assay) positive and negative patients was not statistically significant (P=0.156), while the difference in survival rates between HR-HPV E6/E7 mRNA positive and negative patients, and p16 positive and negative patients were statistically significant (both P<0.05). Multifactorial Cox regression analysis showed that International Federation of Obstetrics and Gynecology (FIGO) staging (HR= 19.875, 95% CI: 1.526-258.833) and parametrial involvement (HR = 14.032, 95% CI: 1.281-153.761) were independent factors influencing the prognosis of patients with ECA. Conclusions HR-HPV E6/E7 mRNA is more reflective of HPV infection in ECA tissue. The efficacy of HR-HPV E6/E7 mRNA and HR-HPV DNA (WTS-PCR assay) in identifying HPVA and NHPVA is similar, with higher sensitivity of HR-HPV DNA and higher specificity of HR-HPV E6/E7 mRNA. HR-HPV DNA is more effective than p16 in identifying HPVA and NHPVA. HPV E6/E7 mRNA and p16 positive ECA patients have better survival rates than negative. [ABSTRACT FROM AUTHOR]

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/E7mRNA阳性与阴性患者, 16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 HPVE6/E7mRNA 更能反映宫颈腺癌组织中HPV的感染情况.HR-HPV E6/E7 mRNA与HR-HPV DNA(WTS-PCR检测)鉴别 HPVA和NHPVA的效能相近,HR-HPV DNA 的灵敏度 较高,而 HR-HPV E6/E7mRNA的特异性较高,HR-HPV DNA鉴别HPVA和NHPVA的效能优于 pl6 表达.HR-HPV E6/E7 mRNA和16表达阳性宫颈腺癌患者的生存率均优于阴性患者. [ABSTRACT FROM AUTHOR]

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