title: Prognostic value of epidermal growth factor receptors in gastric cancer: a survival analysis by Weibull model incorporating long-term survivors.
abstract: BACKGROUND
  There is no consensus about the prognostic role of HER2 expression and that of other members of the EGFR family in gastric cancer patients. The aim of this study was to evaluate the prognostic value of the EGFR family in gastric cancer.
  
  
  METHODS
  This retrospective study included 201 patients with gastric and esophagogastric junction adenocarcinoma stages 0-IV (AJCC 6th edition) who underwent primary tumor resection. Tissues from primary tumors were analyzed by tissue microarray technology and immunohistochemistry. Correlations between receptor expression and clinicopathological characteristics were performed according to the chi-square test. Survival analysis was calculated according to the Weibull model with a mixture model incorporating long-term survivors. Multivariate analysis of prognostic factors was performed by a regression model incorporating long-term survivors with the Weibull distribution.
  
  
  RESULTS
  Membrane expression of HER1, HER2, and HER4 were 9, 17, and 15 %, respectively. No membrane expression of HER3 was observed. Cytoplasmic expression of HER1, HER3, and HER4 were 45, 62, and 24 %, respectively. HER2 and HER3 expression were correlated (p < 0.001) and associated with intestinal-type histology (p = 0.001 and p < 0.001, respectively) and advanced age (p = 0.011 and p = 0.008, respectively). According to a regression model adjusted for age, surgical radicality, surgical modality, Laurén histology, adjuvant therapy, TNM stage, and receptor expressions, only TNM stage showed prognostic influence.
  
  
  CONCLUSIONS
  According to analysis by a parametric model, the EGFR family did not have prognostic influence in the gastric cancer population studied. The data presented showed a correlation between HER2 and HER3 expression, which might suggest a potential role for HER2-HER3 heterodimerization inhibitors.
authors: Department of Medical Oncology, Barretos Cancer Hospital, Str. Antenor Duarte Villela, 1331, Barretos, SP, 14784-400, Brazil, jacome@usp.br.
authors: Alexandre Andrade Anjos
authors: AA
authors: Jácome
authors: Durval R
authors: DR
authors: Wohnrath
authors: Cristovam
authors: C
authors: Scapulatempo Neto
authors: Estela C
authors: EC
authors: Carneseca
authors: Sérgio V
authors: SV
authors: Serrano
authors: Luciano Souza
authors: LS
authors: Viana
authors: João S
authors: JS
authors: Nunes
authors: Edson Z
authors: EZ
authors: Martinez
authors: José Sebastião
authors: JS
authors: Santos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015233:Models, Statistical; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000378:metabolism; D066247:Receptor, ErbB-4; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000601:surgery; D017741:Survivors
chemical_list: D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human; C587689:ERBB4 protein, human