title: HER2/neu testing for anti-HER2-based therapies in patients with unresectable and/or metastatic gastric cancer.
abstract: OBJECTIVE
  To study the HER2 gene amplification or overexpression in patients with advanced gastric cancer (GC) and their association with patient characteristics and patient survival.
  
  
  METHODS
  Tumour tissue samples from 148 patients with advanced GC were studied for HER2 by immunohistochemistry (IHC), fluorescence in situ hybridisation (FISH) and dual colour silver enhanced in situ hybridisation (dc-SISH) methods. Clinicopathological data from all patients were collected. Progression free survival and overall survival were also analysed.
  
  
  RESULTS
  Mean age was 67 (33-83) years; 75% were male subjects, and 51% had intestinal histological type. HER2+ rates were 10.1% (15/148) by IHC, 18.2% (27/148) by FISH+ or 21.6% (32/148) by dc-SISH+. There were significant differences in HER2+ rates according to histological type when FISH (intestinal, 23%; no intestinal, 4%; p<0.0001) or dc-SISH (intestinal, 26%; no intestinal, 6%; p<0.0001) amplification techniques were used. Median overall survival was significantly longer in HER2+ patients despite the determination technique used: IHC (21.4 vs 9.8 months, HR 0.42; p=0.005); FISH (19.6 vs 9.7 months, HR 0.49; p=0.007) or dc-SISH (19.6 vs 9.7 months, HR 0.53; p=0.009). Factors associated with favourable survival in the multivariate analysis were intestinal type and Her2+ determination by IHC, FISH or dc-SISH.
  
  
  CONCLUSIONS
  HER2 gene amplification is significantly associated with patient survival. HER2 gene amplification approaches might be an optimal HER2/neu testing strategy for the selection of HER2+ GC patients who are candidates to be treated with anti-HER2 therapies.
authors.affiliation: Gastrointestinal Cancer Clinical Research Unit, Spanish National Cancer Research Centre, Madrid, Spain. cgomezm@cnio.es
authors.forename: Carlos
authors.initials: C
authors.lastname: Gómez-Martin
authors.forename: Elena
authors.initials: E
authors.lastname: Garralda
authors.forename: M José
authors.initials: MJ
authors.lastname: Echarri
authors.forename: Anabel
authors.initials: A
authors.lastname: Ballesteros
authors.forename: Alberto
authors.initials: A
authors.lastname: Arcediano
authors.forename: José Luis
authors.initials: JL
authors.lastname: Rodríguez-Peralto
authors.forename: Manuel
authors.initials: M
authors.lastname: Hidalgo
authors.forename: Fernando
authors.initials: F
authors.lastname: López-Ríos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D057285:Precision Medicine; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013030:Spain; D013274:Stomach Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human