title: Comparative methodological analysis of erbB-2/HER-2 gene dosage, chromosomal copy number and protein overexpression in breast carcinoma tissues for diagnostic use.
abstract: OBJECTIVE
  This study was performed to test the validity of different methods for determining the status of the erbB-2/HER-2 oncogene in breast cancer tissues for diagnostic use.
  
  
  RESULTS
  Forty formalin-fixed, paraffin-embedded breast carcinomas were investigated by fluorescence in situ and comparative genomic hybridization (FISH, CGH) as well as by immunohistochemistry (IHC) using Dako-HercepTest and CB11 antibody (Ventana). Additionally, competitive-differential polymerase chain reaction (cdPCR) was performed on frozen samples to estimate gene dosage alterations of erbB-2/HER-2. Amplification was detected in 12-23% and protein overexpression in 16-68% of the cases, depending on the methodology and/or the reagent used. Perfect concordance (100%) was found between the results of cdPCR and CB11-IHC, and a 97% concordance between FISH and CB11-IHC. The concordance between Dako-HercepTest and CB11-IHC was 78%: seven of eight 2+ carcinomas with the Dako-HercepTest were classified as nonamplified using FISH.
  
  
  CONCLUSIONS
  Our results indicate that high-level expression as well as normal erbB-2/HER-2 status of breast carcinomas can be detected reliably both by IHC and gene dosage assessment in paraffin material for diagnostic use. However, borderline results, especially those with 2 + immunopositivity, should be interpreted with caution and increased emphasis should be given to other clinical and prognostic information available.
authors: Gerhard-Domagk-Institute of Pathology, Westf. Wilhelms-University Münster, Germany.
authors: A
authors: A
authors: Bánkfalvi
authors: R
authors: R
authors: Simon
authors: B
authors: B
authors: Brandt
authors: H
authors: H
authors: Bürger
authors: I
authors: I
authors: Vollmer
authors: B
authors: B
authors: Dockhorn-Dworniczak
authors: R J
authors: RJ
authors: Lellé
authors: W
authors: W
authors: Boecker
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D018628:Gene Dosage; D018734:Genes, erbB-2; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D005819:Genetic Markers; D018719:Erb-b2 Receptor Tyrosine Kinases