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Claudin-6,一种原始的紧密连接分子表型,在生殖细胞瘤和内脏癌中的表达模式不同。

Distinct expression pattern of claudin-6, a primitive phenotypic tight junction molecule, in germ cell tumours and visceral carcinomas.

机构信息

Department of Pathology and Diagnostic Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

出版信息

Histopathology. 2012 Dec;61(6):1043-56. doi: 10.1111/j.1365-2559.2012.04314.x. Epub 2012 Jul 17.

Abstract

AIMS

This study aimed to clarify claudin-6 expression patterns in cancers.

METHODS AND RESULTS

We surveyed claudin-6 expression by immunohistochemistry using tissue microarray in 860 tumours, including germ cell tumours and major carcinomas. Claudin-6 was expressed consistently in germ cell tumours (28 of 28, 100%), whereas only 64 (8%) of 832 non-germ cell tumours demonstrated claudin-6 expression. Further immunohistochemical study in full tissue sections demonstrated diffuse claudin-6 staining in all seminomas (n=14), embryonal carcinomas (n=10), yolk sac tumours (n=12) and mononuclear trophoblastic cells of choriocarcinomas (n=3), and focal staining in immature epithelial components of immature teratomas (n=6). Additionally, because alpha-fetoprotein (AFP)-producing gastric adenocarcinomas and pulmonary high-grade fetal adenocarcinomas were among the claudin-6 expressing non-germ cell tumours in the microarray studies, we predicted that claudin-6 may be a biomarker for them and studied additional tumours in full sections, which showed claudin-6 expression in AFP-producing gastric adenocarcinomas (18 of 20, 90%) and pulmonary high-grade fetal adenocarcinomas (four of five, 80%). Only one of 11 hepatoblastomas demonstrated focal claudin-6 staining.

CONCLUSIONS

This study demonstrated that claudin-6 is a novel diagnostic marker for primitive germ cell tumours and is also expressed frequently in some cancers with a primitive phenotype.

摘要

目的

本研究旨在阐明紧密连接蛋白 6(claudin-6)在癌症中的表达模式。

方法和结果

我们使用组织微阵列对 860 种肿瘤(包括生殖细胞肿瘤和主要的癌)进行了 claudin-6 的免疫组织化学检测。claudin-6 在生殖细胞肿瘤中一致表达(28/28,100%),而 832 种非生殖细胞肿瘤中仅有 64 种(8%)表达 claudin-6。在全组织切片中的进一步免疫组织化学研究表明,所有精原细胞瘤(n=14)、胚胎癌(n=10)、卵黄囊瘤(n=12)和绒毛膜癌的单核滋养细胞(n=3)中均存在弥漫性 claudin-6 染色,而在未成熟畸胎瘤的未成熟上皮成分(n=6)中存在局灶性染色。此外,因为在微阵列研究中 claudin-6 表达的非生殖细胞肿瘤中包括产生 AFP 的胃腺癌和肺高级别胎儿腺癌,我们预测 claudin-6 可能是它们的生物标志物,并在全切片中研究了其他肿瘤,结果显示在产生 AFP 的胃腺癌(18/20,90%)和肺高级别胎儿腺癌(4/5,80%)中表达 claudin-6。仅 11 例肝母细胞瘤中有 1 例存在局灶性 claudin-6 染色。

结论

本研究表明,claudin-6 是原始生殖细胞肿瘤的新型诊断标志物,在具有原始表型的某些癌症中也经常表达。

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