title: Evidence for hepatocellular differentiation in alpha-fetoprotein-negative gastric adenocarcinoma with hepatoid morphology: a study with in situ hybridisation for albumin mRNA.
abstract: OBJECTIVE
  Hepatoid adenocarcinoma, a putative chemosensitive tumour, is defined as a tumour with aberrant hepatocellular differentiation occurring in extrahepatic organs such as the stomach, usually in the gastrointestinal tract. Differentiation in the hepatocellular direction is usually supported by the production of alpha-fetoprotein (AFP) and, more recently, albumin (ALB) mRNA. We investigated ALB mRNA to address whether adenocarcinoma with hepatoid morphology, regardless of AFP production, can be diagnosed solely by morphological criteria as a hepatoid adenocarcinoma.
  
  
  METHODS
  We performed in situ hybridisation (ISH) and immunohistochemistry (IH) for ALB mRNA on AFP-negative gastric adenocarcinomas with hepatoid morphology. AFP-positive hepatoid adenocarcinomas and AFP-negative conventional gastric adenocarcinomas were also investigated as positive and negative controls, respectively.
  
  
  RESULTS
  All three gastric adenocarcinomas with hepatoid morphology with no evidence of AFP production stained positive for ALB mRNA, thus providing evidence of differentiation in the hepatocellular direction. Three of five cases of AFP-positive hepatoid adenocarcinoma of the stomach were positive for ALB mRNA, while 11 cases of AFP-negative conventional gastric adenocarcinoma were negative.
  
  
  CONCLUSIONS
  The present study demonstrates that, irrespective of AFP production, gastric adenocarcinoma with morphological patterns suggestive of hepatoid differentiation should be diagnosed as hepatoid adenocarcinoma with important prognostic implications.
authors.affiliation: Department of Molecular Pathology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Yana
authors.initials: Y
authors.lastname: Supriatna
authors.forename: Takashi
authors.initials: T
authors.lastname: Kishimoto
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Uno
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nagai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishikura
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000418:Albumins / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D003937:Diagnosis, Differential; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D000509:alpha-Fetoproteins / Q000096:biosynthesis*
chemical_list: D000418:Albumins; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000509:alpha-Fetoproteins