Expression of c-erbB-2 proto-oncogene in extrahepatic cholangiocarcinoma and its clinical significance

Hepatobiliary Pancreat Dis Int. 2007 Aug;6(4):412-5.

Abstract

Background: Many investigators have indicated that overexpression and amplification of the human proto-oncogene c-erbB-2 is an independent prognostic factor for primary tumors. We studied expression of c-erbB-2 protein in tissues from extrahepatic cholangiocarcinoma, tissues peripheral to the carcinoma and normal bile ducts, and discussed the occurrence and development of extrahepatic cholangiocarcinoma. Another aim was to explore possible application of the c-erbB-2 gene for clinical diagnosis, pathological differentiation and treatment of extrahepatic cholangiocarcinomas.

Methods: The c-erbB-2 expression levels from 75 samples of extrahepatic cholangiocarcinoma, 48 samples of tissues peripheral to the carcinoma and 9 samples from normal bile ducts were assayed by immunohistochemical streptavidinbiotin complex (SABC).

Results: The rates of c-erbB-2 expression in extrahepatic cholangiocarcinomas, tissues peripheral to the carcinomas, and normal bile ducts were 80% (60/75), 56% (27/48), and 0% (0/9), respectively. In the extrahepatic cholangiocarcinomas, the expression of c-erbB-2 was directly proportional to the malignant grade and tumor metastasis. The expression rate of c-erbB-2 in tumors with nerve infiltration was significantly higher than in those without nerve infiltration. The expression rates of c-erbB-2 in tumors with histological grade III/IV were significantly higher than in those with histological grade I. The expression of c-erbB-2 was not correlated with the size or position of tumors, blood vessel infiltration or patients' sex or age.

Conclusions: c-erbB-2 was only expressed in extrahepatic cholangiocarcinomas and tissues peripheral to the carcinomas but not in normal bile ducts, indicating that c-erbB-2 may play an important role in the occurrence and development of extrahepatic cholangiocarcinoma. The fact that the expression level of c-erbB-2 was highly correlated with differentiation grade and metastasis of the tumor suggests potential clinical importance of c-erbB-2 as a tumor biomarker in the diagnosis, treatment and prognosis of extrahepatic cholangiocarcinoma.

MeSH terms

  • Aged
  • Bile Duct Neoplasms / metabolism
  • Bile Ducts / metabolism
  • Biotin / chemistry
  • Cholangiocarcinoma / diagnosis
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Mas
  • Receptor, ErbB-2 / biosynthesis*
  • Receptor, ErbB-2 / genetics*
  • Streptavidin / chemistry

Substances

  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Biotin
  • Streptavidin
  • Receptor, ErbB-2