title: Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1 and 3 in Gastric and Esophageal Adenocarcinoma.
abstract: BACKGROUND
  Gastric and esophageal adenocarcinomas are major global cancer burdens. These cancer forms are characterized by a poor prognosis and a modest response to chemo- radio- and targeted treatment. Hence there is an obvious need for further enhanced diagnostic and treatment strategies. The aim of this study was to examine the expression and prognostic impact of human epidermal growth factor receptor 1 (HER1/EGFR) and 3 (HER3), as well as the occurrence of EGFR and KRAS mutations in gastric and esophageal adenocarcinoma.
  
  
  METHODS
  Immunohistochemical expression of EGFR and HER3 was analysed in all primary tumours and a subset of lymph node metastases in a consecutive cohort of 174 patients with adenocarcinoma of the stomach, cardia and esophagus. The anti-HER3 antibody used was validated by siRNA-mediated knockdown, immunohistochemistry and quantitative real-time PCR. EGFR and KRAS mutation status was analysed by pyrosequencing tecchnology.
  
  
  CONCLUSIONS
  High EGFR expression was an independent risk factor for shorter overall survival (OS), whereas high HER3 expression was associated with a borderline significant trend towards a longer OS. KRAS mutations were present in only 4% of the tumours and had no prognostic impact. All tumours were EGFR wild-type. These findings contribute to the ongoing efforts to decide on the potential clinical value of different HERs and druggable mutations in gastric and esophageal adenocarcinomas, and attention is drawn to the need for more standardised investigational methods.
authors: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden.
authors: Charlotta
authors: C
authors: Hedner
authors: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden.
authors: David
authors: D
authors: Borg
authors: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden.
authors: Björn
authors: B
authors: Nodin
authors: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden.
authors: Emelie
authors: E
authors: Karnevi
authors: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden.
authors: Karin
authors: K
authors: Jirström
authors: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, 221 85, Lund, Sweden.
authors: Jakob
authors: J
authors: Eberhard
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D014408:Biomarkers, Tumor; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000378:metabolism; D009154:Mutation; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D020893:Receptor, ErbB-3