高危型人乳头瘤病毒E6/E7信使核糖核酸原位杂交技术在子宫颈管腺性肿瘤中的应用：与p16和Ki67免疫组化的性能比较

High-risk HPV E6/E7 mRNA in situ hybridization in endocervical glandular neoplasia: performance compared with p16 and Ki67 immunochemistry.

作者信息

Chen Tingting, Li Jing, Wang Shunni, Ning Yan, Zhou Xianrong, Wang Yiqin

机构信息

Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University No. 128, Shenyang Road, Shanghai 200082, China.

出版信息

Am J Transl Res. 2019 Oct 15;11(10):6498-6506. eCollection 2019.

PMID:31737201

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6834507/

Abstract

OBJECTIVE

HR-HPV E6/E7 mRNA in situ hybridization (HR-HPV RISH) can detect HPV-driven endocervical glandular neoplasia. Our aim was to compare its diagnostic performance with the conventional p16 and Ki67 immunochemistry (IHC).

METHODS

HR-HPV RISH and IHC were performed in normal cervix (n = 70), reactive cervix (n = 60), adenocarcinoma in situ (AIS) (n = 92), endocervical adenocarcinoma (ECA) and adenosquamous carcinoma (n = 21) samples (n = 163). The sensitivities and specificities of the three markers were compared in the benign, AIS, HPV-associated adenocarcinoma (HPVA) and non HPV-associated adenocarcinoma (NHPVA) samples, and in 39 endocervical curettage specimens containing endometrial and HPV-associated neoplastic glands. Finally, the inter-observer agreement rate for the three markers were calculated.

RESULTS

The sensitivities of HR-HPV RISH, P16 and Ki67 were 100% for the HPV-related glandular neoplasia and HPVAs in ECAs, while the specificity of HR-HPV RISH (100%) were higher than the other two (88.89% and 17.77% for P16 and Ki67 respectively) in the HPVAs. Furthermore, HR-HPV RISH was more specific than either p16 block+ or Ki67 in the endocervical curettage specimens and in HPVAs with poor differentiation. Finally, the inter-observer agreement for HR-HPV RISH was higher than that for the morphological, p16 block+ and Ki67 markers (99.67% vs. 95.10%, 99.35% and 90.85% respectively).

CONCLUSIONS

HR-HPV RISH is highly sensitive and specific for HPV-driven endocervical glandular neoplasia compared to p16 and Ki67, and should be incorporated for ECA diagnosis.

摘要

目的

高危型人乳头瘤病毒E6/E7信使核糖核酸原位杂交（HR-HPV RISH）可检测人乳头瘤病毒驱动的宫颈管腺上皮瘤变。我们的目的是将其诊断性能与传统的p16和Ki67免疫组化（IHC）进行比较。

方法

对正常宫颈（n = 70）、反应性宫颈（n = 60）、原位腺癌（AIS）（n = 92）、宫颈管腺癌（ECA）和腺鳞癌（n = 21）样本（n = 163）进行HR-HPV RISH和IHC检测。比较这三种标志物在良性、AIS、人乳头瘤病毒相关腺癌（HPVA）和非人乳头瘤病毒相关腺癌（NHPVA）样本以及39份包含子宫内膜和人乳头瘤病毒相关肿瘤性腺体的宫颈管刮除标本中的敏感性和特异性。最后，计算三位观察者对这三种标志物的一致率。

结果

HR-HPV RISH、P16和Ki67对ECA中与人乳头瘤病毒相关的腺上皮瘤变和HPVA的敏感性均为100%，而在HPVA中，HR-HPV RISH的特异性（100%）高于其他两者（P16和Ki67分别为88.89%和17.77%）。此外，在宫颈管刮除标本和分化差的HPVA中，HR-HPV RISH比p16阻滞+或Ki67更具特异性。最后，HR-HPV RISH的观察者间一致性高于形态学、p16阻滞+和Ki67标志物（分别为99.67%对95.10%、99.35%和90.85%）。