title: Adenocarcinoma of gallbladder: an immunohistochemical profile and comparison with cholangiocarcinoma.
abstract: OBJECTIVE
  Cholangiocarcinomas display intestinal and pyloric gland metaplasia-cell phenotypes. Those that arise in chronically inflamed (fluke infested) bile ducts more frequently express the intestinal metaplasia-cell phenotype and p53 than sporadic cholangiocarcinomas. We wished to determine if adenocarcinomas of the gallbladder display a similar profile.
  
  
  METHODS
  Adenocarcinoma, adenoma, and dysplastic and metaplastic epithelia were studied in 55 gallbladders. Serial paraffin sections were stained for five foregut antigens characteristically present in pyloric gland metaplasia, three intestinal-specific antigens and p53. Antigen expression was compared with that shown by 65 fluke-associated and 47 sporadic cholangiocarcinomas.
  
  
  RESULTS
  Pyloric gland metaplasia in gallbladders with chronic cholecystitis invariably displayed the five foregut antigens. The frequency of expression of these five antigens by the gallbladder cancers and cholangiocarcinomas did not differ significantly. An intestinal goblet-cell marker and p53 were more frequently expressed by gallbladder carcinoma (59% and 45%, respectively) and fluke-associated cholangiocarcinoma (45% and 46%) than by sporadic cholangiocarcinoma (17% and 23%). K20 was more frequently expressed by gallbladder carcinoma (52%) than either fluke-associated (21%) or sporadic (17%) cholangiocarcinoma. Dysplastic epithelium and adenomas also displayed the pyloric gland and intestinal metaplasia-cell phenotypes. Cells staining for pyloric gland metaplasia-cell phenotypes were distinct from the intestinal metaplasia-cell phenotypes when present together in a gallbladder carcinoma, cholangiocarcinoma, dysplastic epithelium or adenoma.
  
  
  CONCLUSIONS
  Adenocarcinomas of gallbladder generally arise from a foregut cell lineage via a metaplasia-dysplasia-carcinoma sequence. A background of chronic inflammation increases the frequency of expression of an intestinal goblet-cell phenotype and p53 in the cancers.
authors.affiliation: Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Norman Richard
authors.initials: NR
authors.lastname: Hughes
authors.forename: Prithi S
authors.initials: PS
authors.lastname: Bhathal
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D002908:Chronic Disease; D018450:Disease Progression; D005211:Fascioliasis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D005260:Female; D005704:Gallbladder / Q000378:metabolism / Q000473:pathology; D005706:Gallbladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D006505:Hepatitis / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008099:Liver / Q000473:pathology; D008297:Male; D008679:Metaplasia / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D011230:Precancerous Conditions / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53