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

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Embryonal / metabolism
  • Carcinoma, Embryonal / pathology
  • Claudins / metabolism*
  • Endodermal Sinus Tumor / metabolism
  • Endodermal Sinus Tumor / pathology
  • Female
  • Fetus / metabolism
  • Fetus / pathology
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Neoplasms, Germ Cell and Embryonal / metabolism*
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Phenotype*
  • Seminoma / metabolism
  • Seminoma / pathology
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Testicular Neoplasms / metabolism
  • Testicular Neoplasms / pathology
  • Tight Junctions / pathology*
  • alpha-Fetoproteins / metabolism

Substances

  • Biomarkers, Tumor
  • Claudins
  • alpha-Fetoproteins
  • claudin 6