高危型人乳头状瘤病毒E6/E7 mRNA原位杂交技术在宫颈上皮内瘤变分级中的应用价值

Value of high-risk HPV E6/E7 mRNA in situ hybridization in grading of cervical intraepithelial neoplasia

目的探讨高危型人乳头状瘤病毒(HPV)E6/E7 mRNA原位杂交技术在宫颈上皮内瘤变(CIN)分级诊断中的应用价值。方法收集四川大学华西第二医院2019年7月至2020年6月组织病理诊断为CIN与宫颈鳞状细胞癌的病例共261例,其中CIN1级60例、CIN2级41例、CIN3级51例、鳞癌72例和形态学正常的宫颈对照组织37例(HPV阴性10例、阳性27例)。将所有病理组织制成组织芯片,分别进行HE染色、HPV E6/E7 mRNA原位杂交检测及p16免疫组织化学染色,在光镜下完成染色判读,并统计分析其阳性率及阳性模式。结果HPV mRNA原位杂交在CIN1级中主要表现为鳞状上皮基底至中层细胞核与质的点状染色(≤BME)及伴表层细胞内弥散整个核的片状染色(supD),即≤BME+supD模式;在CIN2级中主要表现为基底直至中层之上但未达上皮全层的细胞核与质的点状染色模式(>BME)和部分伴supD染色的模式,即>BME+SupD模式;CIN3级主要表现为>BME模式,且点状染色分布于上皮全层。在CIN1级、2级和3级中,上述3种染色模式差异有统计学意义(P<0.05)。结论HPV mRNA原位杂交技术有助于CIN的准确诊断与分级,且有着比p16免疫组织化学染色更佳的特异性。

Objective To investigate the value of high-risk HPV E6/E7 mRNA in situ hybridization in the grading of cervical squamous intraepithelial neoplasia(CIN).Methods A total of 261 cases with diagnosis of CIN and cervical squamous cell carcinoma(SCC)at west China University Second Hospital,Sichuan University from July 2019 to June 2020 were collected,including 60 cases of CIN1,41 cases of CIN2,51 cases of CIN3,72 cases of SCC,and 37 cases of normal cervical control tissue(10 HPV negative and 27 HPV positive).All pathologic tissues were made into tissue microarrays,and HE staining,HPV E6/E7 mRNA in situ hybridization(ISH)and p16 immunohistochemical(IHC)staining were performed respectively.The staining was assessed by light microscopy,and the positive rate and positive pattern were analyzed statistically.Results HPV mRNA ISH in CIN1 mainly showed spot staining in predominantly basal to mid-epithelial layers(≤BME)with a diffuse nuclear signals in the superficial layer(supD),that is,the pattern of≤BME+supD;in CIN2,it mainly showed spot staining in predominantly basal to above mid-epithelial but not the full layer(>BME)and some cases with supD staining,that is,the pattern of>BME+supD;In CIN3,the mainly pattern was>BME,and the spot staining was distributed throughout the epithelium.In CIN1,CIN2 and CIN3,there were significantly statistical differences among the above three staining patterns(P<0.05).Conclusions HPV mRNA ISH contributes to the accurate diagnosis and grading of CIN,and has better specificity than p16 IHC staining.