Immunophenotype analysis using CLDN18, CDH17, and PAX8 for the subcategorization of endocervical adenocarcinomas in situ: gastric-type, intestinal-type, gastrointestinal-type, and Mullerian-type
Immunophenotype analysis using CLDN18, CDH17, and PAX8 for the subcategorization of endocervical adenocarcinomas in situ: gastric-type, intestinal-type, gastrointestinal-type, and Mullerian-type
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DOI：
10.1007/s00428-019-02739-x
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发表时间：
2020-04-01
期刊：
影响因子：
3.5
通讯作者：
Ota, Hiroyoshi
中科院分区：
文献类型：
--
作者：
Asaka, Shiho;Nakajima, Tomoyuki;Ota, Hiroyoshi
宫颈腺癌的分类系统，重点是高风险的人乳头瘤病毒（HPV）的检测，最近已经开发出来。然而，每个ECA亚型的前驱病变和免疫组化标记物，有效地亚分类ECA与胃和肠分化尚未得到充分的描述。在这里，我们的目的是通过免疫表型对宫颈内原位腺癌（AIS）进行亚类分类，并描述每种AIS亚型的组织病理学特征。我们使用三种细胞系特异性标志物（CLDN 18，胃上皮细胞; CDH 17，肠上皮细胞; PAX 8，苗勒氏上皮细胞）对36例AIS和25例小叶宫颈内腺增生（LEGH）样本进行了化学分析。AIS的免疫表型分为胃型（G-AIS; n = 2）、胃肠道型（I-AIS; n = 10）、胃肠道型（GI-AIS; n = 3）、苗勒氏型（M-AIS; n = 18）和AIS，未另行说明（AIS-NOS; n = 3）。所有25例LEGH均被归类为胃型。G-AIS细胞质呈淡嗜酸性或透明，有少量顶端粘蛋白，有丝分裂小体较少。I-AIS包含不同数量的杯状细胞型肿瘤细胞。GI-AIS表现为G-AIS和I-AIS的中间或混合特征。与通常类型的ECA一样，M-AIS的典型特征是粘蛋白耗尽;然而，一些病变具有丰富的胞质粘蛋白。高危型HPV在大多数AIS中检出，但在100%（2/2）的G-AIS、10%（1/10）的I-AIS和6%（1/18）的M-AIS病变中均为阴性。总之，免疫表型定义的AIS亚型具有不同的组织病理学和病因学特征。因此，用CLDN 18、CDH 17和PAX 8进行免疫分型可能提高ECA的组织病理学分类的诊断准确性。
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, Mullerian 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), Mullerian-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.