Department of Pathology and Diagnostic Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Histopathology. 2012 Dec;61(6):1043-56. doi: 10.1111/j.1365-2559.2012.04314.x. Epub 2012 Jul 17.
This study aimed to clarify claudin-6 expression patterns in cancers.
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.
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.
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。
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。
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。