Impact of epidermal growth factor receptor protein and gene alteration on Taiwanese hepatocellular carcinomas

J Gastroenterol Hepatol. 2015 Sep;30(9):1397-404. doi: 10.1111/jgh.12944.

Abstract

Background and aim: Epidermal growth factor receptor (EGFR) overexpression is associated with disease progression and poor survival in a variety of solid tumors. The role of EGFR in hepatocellular carcinoma (HCC) remains controversial.

Methods: One hundred thirty-eight HCCs were analyzed for total EGFR (t-EGFR) and phospho-EGFR (p-EGFR) expression and gene amplification using immunohistochemistry and fluorescence in situ hybridization. The role of EGFR was analyzed in relation to the clinicopathological features.

Results: Weak to strong p-EGFR immunostaining was noted in 42 of the 138 HCCs. p-EGFR expression correlated with alcoholism (P = 0.03) and chronic hepatitis B infection (P = 0.041). There was no correlation between t-EGFR expression and any of the clinicopathological features. Amplification of the EGFR gene was not identified in the 138 HCCs, but 39.1% of the HCCs showed balanced polysomy of both the EGFR gene and centromere 7. Moreover, 65 tumors showed > 2.2 copies per tumor cell. EGFR copy number gain (CNG) was significantly correlated with gender (P = 0.0491), tumor grade (P = 0.006), and vascular invasion (P = 0.005). HCCs with EGFR CNG also had a poor recurrence-free survival (RFS), as compared with HCCs without EGFR CNG (P = 0.031). When exploring the impact of gender, a significant association of EGFR CNG was found with tumor grade (P = 0.044) and cirrhosis (P = 0.015) exclusively in the male group only; however, the OS and RFS analysis show no significant difference between male and female groups.

Conclusions: EGFR CNG was related to crucial clinicopathological features and early recurrence, indicating that EGFR CNG might be a poor prognosis factor for Taiwanese HCC.

Keywords: epidermal growth factor receptor; fluorescence in situ hybridization; hepatocellular carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • ErbB Receptors / analysis*
  • ErbB Receptors / genetics*
  • ErbB Receptors / physiology
  • Female
  • Gene Dosage*
  • Gene Expression / genetics*
  • Humans
  • Liver / metabolism
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Prognosis
  • Taiwan

Substances

  • ErbB Receptors