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Comparative methodological analysis of erbB‐2/HER‐2 gene dosage, chromosomal copy number and protein overexpression in breast carcinoma tissues for diagnostic use
Author(s) -
Bánkfalvi À,
Simon R,
Brandt B,
Bürger H,
Vollmer I,
DockhornDworniczak B,
Lellé RJ,
Boecker W
Publication year - 2000
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1046/j.1365-2559.2000.00984.x
Subject(s) - concordance , immunohistochemistry , fluorescence in situ hybridization , breast cancer , gene duplication , breast carcinoma , pathology , carcinoma , gene dosage , polymerase chain reaction , biology , medicine , cancer , gene , gene expression , chromosome , genetics
Aims : 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. Methods and 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 TM 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 TM and CB11‐IHC was 78%; seven of eight 2 + carcinomas with the Dako‐HercepTest TM 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.