Morphometric and immunohistochemical study of cholangiolocellular carcinoma: comparison with non-neoplastic cholangiole, interlobular duct and septal duct

J Hepatobiliary Pancreat Sci. 2012 May;19(3):289-96. doi: 10.1007/s00534-011-0483-5.

Abstract

Background/purpose: The origin of cholangiolocellular carcinoma (CoCC) is still controversial. To solve this problem, morphometric and immunohistochemical features of CoCC were examined.

Materials and methods: Cancerous ducts: 15 CoCC lesions from 13 resected and two autopsied cases. Non-neoplastic ducts: 20 specimens of non-cancerous areas of eight resected CoCC cases and of 12 resected hepatocellular carcinoma (HCC) cases. From these specimens, cholangioles, interlobular ducts of small size (ILD-S), interlobular ducts of medium size (ILD-M) and septal ducts were randomly selected. MORPHOMETRY: The outer and inner diameters of these ducts were measured. Immunohistochemistry: two hepatocyte markers [Hep Par 1 and α-fetoptotein (AFP)], two cholangiocyte markers (cytokeratin CK7, CK19), a marker for mucin (Muc1), a hepatic stem/progenitor cell marker (c-Kit) and epithelial membrane antigen (EMA) were used.

Results: Morphometry: both mean values of the outer and inner diameters of CoCC were far larger than those of cholangioles, and showed intermediate values between those of ILD-S and ILD-M. Immunohistochemistry: all ducts of CoCCs were negative for the two hepatocyte markers and positive for CK 7. Most CoCC ducts were positive for CK 19. Positive rate of c-Kit of cholangiole was most remote from that of CoCC. The positive rates of EMA in the membranous area of ducts were similarly very high in CoCC, cholangiole and ILD-S.

Conclusion: These results suggest that CoCCs may originate from ILDs.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / pathology*
  • Bile Ducts, Intrahepatic / metabolism
  • Bile Ducts, Intrahepatic / pathology*
  • Biomarkers, Tumor / metabolism*
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / pathology*
  • Diagnosis, Differential
  • Female
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Immunohistochemistry
  • Keratin-19 / metabolism
  • Keratin-7 / metabolism
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Mucin-1 / metabolism
  • Proto-Oncogene Proteins c-kit / metabolism
  • Retrospective Studies
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • Keratin-19
  • Keratin-7
  • Mucin-1
  • Proto-Oncogene Proteins c-kit