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

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.