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

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.