title: FISH for HER-2/neu in breast cancer: standardization makes the difference!
abstract: BACKGROUND
  Overexpression of HER-2/neu oncogene in breast cancer patients is correlated with disease free survival (DFS) and overall survival (OS). The most commonly used methods for the detection of HER-2/neu status are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). However, therse is a lot of controversy with regard to the best method. Most of the FISH studies chose arbitrary cut-off levels for positive results (10%) and had no validation.
  
  
  OBJECTIVE
  In order to address these issues, we designed a pilot study of 38 samples with known IHC status representing all 4 categories.
  
  
  METHODS
  FISH was performed using Vysis Pathvysion probe. For validation, 5 cases of reduction mammoplasty were analyzed using same protocols.
  
  
  RESULTS
  Our results showed significant discordance between FISH and IHC. The rate of discordance was much higher in the 0, 1+, and 2+ categories compared to published literature. This could be due to the lower cut-off rates for positive amplification established by validation in our study (5.7% vs 10%). Our analysis showed that FISH positive and IHC negative patients have a poor prognosis in terms of DFS and OS compared to FISH negative and IHC negative patients. Further, our results also showed that IHC in comparison to FISH has a comparable specificity (98%), but has a very low sensitivity (46%).
  
  
  CONCLUSIONS
  Based on these results, we consider FISH to be the gold standard for detecting HER-2/neu status in breast cancer.
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Sumita
authors.initials: S
authors.lastname: Gokhale
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gatalica
authors.forename: Amin
authors.initials: A
authors.lastname: Mohammad
authors.forename: A I
authors.initials: AI
authors.lastname: Rampy
authors.forename: V N
authors.initials: VN
authors.lastname: Velagaleti Gopalrao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence / Q000592:standards*; D008875:Middle Aged; D015588:Observer Variation; D010865:Pilot Projects; D012015:Reference Standards; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis