title: Impact of epidermal growth factor receptor protein and gene alteration on Taiwanese hepatocellular carcinomas.
abstract: OBJECTIVE
  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.
authors.affiliation: Cancer Diagnostic Laboratory, Lin-Kou Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
authors.forename: Yu-Hung
authors.initials: YH
authors.lastname: Su
authors.affiliation: Department of Pathology, Lin-Kou Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Tao-Yuan, Taiwan.
authors.forename: Kwai-Fong
authors.initials: KF
authors.lastname: Ng
authors.affiliation: Department of General Surgery, Lin-Kou Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Tao-Yuan, Taiwan.
authors.forename: Ming-Chin
authors.initials: MC
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Lin-Kou Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Tao-Yuan, Taiwan.
authors.forename: Ting-Jung
authors.initials: TJ
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Lin-Kou Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Tao-Yuan, Taiwan.
authors.forename: Ta-Sen
authors.initials: TS
authors.lastname: Yeh
authors.affiliation: Department of General Surgery, Lin-Kou Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Tao-Yuan, Taiwan.
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Lee
authors.affiliation: Department of Pathology, Lin-Kou Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Tao-Yuan, Taiwan.
authors.forename: Yong-Shiang
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Department of Biobank, Lin-Kou Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Tao-Yuan, Taiwan.
authors.forename: Tsung-Han
authors.initials: TH
authors.lastname: Hsieh
authors.affiliation: Department of Hepato-Gastroenterology, Lin-Kou Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Tao-Yuan, Taiwan.
authors.forename: Chun-Yen
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Liver Research Center, Lin-Kou Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Tao-Yuan, Taiwan.
authors.forename: Chau-Ting
authors.initials: CT
authors.lastname: Yeh
authors.affiliation: Cancer Diagnostic Laboratory, Lin-Kou Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.|Department of Pathology, Lin-Kou Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Tao-Yuan, Taiwan.
authors.forename: Tse-Ching
authors.initials: TC
authors.lastname: Chen
mesh_terms: D044466:Asian People; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics* / Q000502:physiology; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D013624:Taiwan
chemical_list: D066246:ErbB Receptors
keywords: epidermal growth factor receptor; fluorescence in situ hybridization; hepatocellular carcinoma