title: [HER-2 oncogene amplification assessment in invasive breast cancer by dual-color in situ hybridization (dc-CISH): a comparative study with fluorescent in situ hybridization (FISH)].
abstract: OBJECTIVE
  The amplification of the gene encoding for the human epidermal growth factor receptor 2 (HER-2 oncogene), located on chromosome 17 (17q21-q22), or the overexpression of this receptor have prognostic and therapeutic implications in invasive breast cancer. An evaluation of the HER-2 status by immunohistochemistry (IHC) is performed on all invasive breast cancer cases. Fluorescent in situ hybridization (FISH) is considered as the gold standard for the detection of HER-2 gene amplification for IHC equivocal cases (score 2+). A more recent in situ hybridization technique, the dual-color chromogenic in situ hybridization (dc-CISH), has been proposed as an alternative to FISH. The aim of this study was to measure the correlation between dc-CISH and FISH for HER-2 oncogene amplification assessment in invasive breast cancer.
  
  
  RESULTS
  We built four tissue micro-array (TMA) blocs with 100 breast invasive cancer cases that had been previously tested by IHC for HER-2 detection: 10 score 0 cases, 10 score 3+cases, 39 score 1+and 41 score 2+cases. Both FISH and dc-CISH techniques were applied on all TMA cases as well as on two additional slides serving as controls. Interpretation of dc-CISH was carried out by a pathologist using an optical microscope. For FISH, the interpretation was done by a professional from the medical genetics department using a fluorescent microscope linked to a computer system for image capturing and analysis. The interpretation of the HER-2/CEN-17 ratio for both tests was in accordance with the values of the updated recommendations from the Canadian National Consensus Meeting on HER-2/neu testing in breast cancer and from the ASCO/CAP. Among the 100 cases initially included in the study, eight were excluded from the analysis due to sampling or technical flaws. From the 92 remaining cases, we obtained a concordance of 97.8% (90/92 cases) between the two techniques (Kappa coefficient 0.97, 95% confidence interval). The correlation coefficient (rho) between ratios was estimated at 0.57.
  
  
  CONCLUSIONS
  This study shows a strong concordance between FISH and dc-CISH techniques and indicates that dc-CISH is a good alternative method for HER-2 gene amplification assessment in breast cancer.
authors.affiliation: Département de pathologie, centre hospitalier de l'université de Sherbrooke (CHUS), Québec, Canada.
authors.forename: Abbas
authors.initials: A
authors.lastname: Akhdar
authors.forename: Marc
authors.initials: M
authors.lastname: Bronsard
authors.forename: Renald
authors.initials: R
authors.lastname: Lemieux
authors.forename: Sameh
authors.initials: S
authors.lastname: Geha
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics / Q000473:pathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics / Q000648:ultrastructure; D005260:Female; D005456:Fluorescent Dyes; D005784:Gene Amplification; D018734:Genes, erbB-2; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D015203:Reproducibility of Results; D013194:Staining and Labeling
chemical_list: D005456:Fluorescent Dyes