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HER2/neu testing for anti-HER2-based therapies in patients with unresectable and/or metastatic gastric cancer
  1. Carlos Gómez-Martin1,
  2. Elena Garralda1,
  3. M José Echarri2,
  4. Anabel Ballesteros3,
  5. Alberto Arcediano4,
  6. José Luis Rodríguez-Peralto5,
  7. Manuel Hidalgo1,
  8. Fernando López-Ríos6
  1. 1Gastrointestinal Cancer Clinical Research Unit, Spanish National Cancer Research Centre, Madrid, Spain
  2. 2Medical Oncology Unit, Hospital Universitario Severo Ochoa, Madrid, Spain
  3. 3Medical Oncology Unit, Hospital Universitario de la Princesa, Madrid, Spain
  4. 4Medical Oncology Division, Hospital Universitario de Gualajara, Guadalajara, Spain
  5. 5Pathology Department, Hospital Universitario 12 de Octubre, Madrid, Spain
  6. 6Laboratorio de Dianas Terapéuticas, Centro Integral Oncológico ‘Clara Campal’, Hospital Universitario Madrid Sanchinarro, Universidad San Pablo-CEU, Facultad de Medicina, Madrid, Spain
  1. Correspondence to Dr Carlos Gómez-Martin, Gastrointestinal Cancer Clinical Research Unit, Clinical Research Programme, Spanish National Cancer Research Centre (CNIO), Fuenlabrada University Hospital, Camino del Molino 2, Fuenlabrada 28942, Madrid, Spain; cgomezm{at}cnio.es

Abstract

Aim To study the HER2 gene amplification or overexpression in patients with advanced gastric cancer (GC) and their association with patient characteristics and patient survival.

Patients and 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.

Conclusion 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.

  • In situ hybridisation
  • gastric cancer
  • immunohistochemistry
  • molecular oncology
  • breast cancer
  • CERB 2
  • ovarian tumour
  • lung cancer
  • pleura

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Footnotes

  • Funding Financial support of research provided by Roche Farma Spain who have no role in conception and design of this research, analysis and interpretation of data, drafting of the article or final approval of the version to be published.

  • Competing interests None.

  • Patient consent We report our results in a series of gastric cancer patients treated for their disease. There are no personal data in our manuscript. All patients who are alive were provided with an Informed consent document to allow the researchers perform this study by using their tumoral samples.

  • Ethics approval The ethics approval was provided by the Ethics Committee/Institutional Review Board at Centro Integral de Oncologia Clara Campal.

  • Provenance and peer review Not commissioned; externally peer reviewed.