title: Vascular endothelial growth factor expression is an independent poor prognostic factor for human epidermal growth factor receptor 2 positive gastric cancer.
abstract: The positive expression of human epidermal growth factor receptor 2 (HER-2) is phenotypically associated with differentiated gastric cancer (GC) and is a prognostic factor for resectable GC. The aim of this study was to explore the clinical significance of vascular endothelial growth factor (VEGF), protein kinase B, and p38 mitogen-activated protein kinase (MAPK) regarding outcome in patients with HER-2 positive GC, and to analyze the relationship between these molecules and clinicopathologic parameters.
  
  
  
  Between January 2001 and December 2012, radical-intent gastrectomy specimens from GC patients were evaluated for HER-2 expression by immunohistochemistry (IHC); and with HER-2 expression levels of 2+ were further subjected to fluorescence in situ hybridization analysis. HER-2 positivity was defined by a HER-2 3+ score on IHC or a HER-2 2+ score on IHC and HER-2 amplification by fluorescence in situ hybridization. The expression of VEGF, phosphorylated protein kinase B, and phosphorylated p38 MAPK in HER-2 positive specimens was scored using IHC.
  
  
  
  Fifty-four patients with HER-2 positive stage I-III GCs were identified. Univariate analysis of prognostic factors showed that tumor differentiation, the presence of vascular invasion, and overexpression of p-p38 MAPK, and VEGF significantly affected prognosis. Multivariate analysis identified vascular invasion (hazard ratio = 2.704; 95% confidence interval = 1.074-7.088; P < 0.033) and the overexpression of VEGF (hazard ratio = 2.760; 95% confidence interval = 1.083-6.753; P < 0.035) to be independent prognostic predictors of HER-2 positive GC.
  
  
  
  VEGF overexpression and the presence of vascular invasion were independent poor prognostic factors for HER-2 positive GCs.
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: hsujt2813@adm.cgmh.org.tw.
authors.forename: Jun-Te
authors.initials: JT
authors.lastname: Hsu
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Tai-Di
authors.initials: TD
authors.lastname: Chen
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Huei-Chieh
authors.initials: HC
authors.lastname: Chuang
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Shih-Chiang
authors.initials: SC
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Puo-Hsien
authors.initials: PH
authors.lastname: Le
authors.affiliation: Department of Gastroenterology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Tsung-Hsing
authors.initials: TH
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Lin
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Ta-Sen
authors.initials: TS
authors.lastname: Yeh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D008297:Male; D008875:Middle Aged; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D013624:Taiwan / Q000453:epidemiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Angiogenesis; Gastric cancer; HER-2; Prognostic factor; VEGF