Comparative methodological analysis of erbB-2/HER-2 gene dosage, chromosomal copy number and protein overexpression in breast carcinoma tissues for diagnostic use.
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.
Bánkfalvi
A
A
Gerhard-Domagk-Institute of Pathology, Westf. Wilhelms-University Münster, Germany.
Simon
R
R
Brandt
B
B
Bürger
H
H
Vollmer
I
I
Dockhorn-Dworniczak
B
B
Lellé
R J
RJ
Boecker
W
W
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*
D017931:DNA Primers; D004273:DNA, Neoplasm; D005819:Genetic Markers; D018719:Erb-b2 Receptor Tyrosine Kinases