A classification system for invasive endocervical adenocarcinoma (ECA) focusing on high-risk human papillomavirus (HPV) detection has been recently developed. However, precursor lesions of each ECA subtype and immunohistochemical markers that effectively subcategorize ECAs with gastric and intestinal differentiation have not been fully described. Here, we aimed to subcategorize endocervical adenocarcinoma in situ (AIS) by immunophenotype and to characterize the histopathology of each AIS subtype. We immunohistochemically analyzed 36 AIS and 25 lobular endocervical glandular hyperplasia (LEGH) samples using three cell lineage-specific markers (CLDN18, gastric epithelial cells; CDH17, intestinal epithelial cells; and PAX8, Müllerian epithelial cells). The AISs were immunophenotypically classified as gastric-type (G-AIS; n = 2), intestinal-type (I-AIS; n = 10), gastrointestinal-type (GI-AIS; n = 3), Müllerian-type (M-AIS; n = 18), and AIS, not otherwise specified (AIS-NOS; n = 3). All 25 LEGHs were categorized as gastric-type. G-AIS had pale eosinophilic or clear cytoplasm with a small amount of apical mucin and fewer mitotic bodies. I-AIS comprised various numbers of goblet cell-type tumor cells. GI-AIS showed intermediate or mixed features of G-AIS and I-AIS. M-AIS, as with the usual-type ECA, was typically characterized by mucin depletion; however, several lesions had abundant cytoplasmic mucin. High-risk HPV was detected in most AISs but was negative in 100% (2/2) of G-AIS, 10% (1/10) of I-AIS, and 6% (1/18) of M-AIS lesions. In summary, the AIS subtypes defined by immunophenotype had distinct histopathological and etiological characteristics. Thus, immunophenotyping with CLDN18, CDH17, and PAX8 might improve the diagnostic accuracy of histopathological classifications of ECAs.

中文翻译：

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使用CLDN18，CDH17和PAX8对宫颈内腺癌进行原位亚型分类的免疫表型分析：胃型，肠型，胃肠型和Müllerian型。

最近开发了一种针对高侵害性人乳头瘤病毒（HPV）检测的浸润性宫颈内腺癌（ECA）分类系统。然而，尚未充分描述每种ECA亚型的前体病变和有效分类ECA的胃和肠分化的免疫组化标记。在这里，我们旨在通过免疫表型对宫颈内膜腺癌（AIS）进行亚分类，并描述每种AIS亚型的组织病理学特征。我们使用三种细胞谱系特异性标记物（CLDN18，胃上皮细胞； CDH17，肠上皮细胞；以及PAX8，Müllerian上皮细胞）免疫组化分析了36例AIS和25例小叶宫颈内膜增生（LEGH）样品。根据免疫表型将AIS归类为胃型（G-AIS； n = 2），肠型（I-AIS; n = 10），肠胃型（GI-AIS; n = 3），苗勒氏型（M-AIS; n = 18）和未另作说明的AIS（AIS-NOS; n = 3）。所有25个LEGH均归类为胃型。G-AIS的嗜酸性粒细胞呈浅色或胞浆澄清，顶端的粘蛋白少，有丝分裂体少。I-AIS包含各种杯状细胞型肿瘤细胞。GI-AIS显示了G-AIS和I-AIS的中间或混合特征。与通常的ECA一样，M-AIS的典型特征是粘液消耗。然而，一些病变具有丰富的细胞质粘蛋白。在大多数AIS中检测到高危HPV，但在100％（2/2）的G-AIS，10％（1/10）的I-AIS和6％（1/18）的M-AIS病变中呈阴性。总之，由免疫表型定义的AIS亚型具有独特的组织病理学和病因学特征。从而，