HER-2/neu analysis in breast cancer bone metastases.
BACKGROUND
HER-2 is the target for antibody-based treatment of breast cancer (trastuzumab), which is highly successful in both advanced disease and the adjuvant setting. HER-2 can be analysed by fluorescence in situ hybridisation (FISH) for gene amplification or immunohistochemistry (IHC) for protein overexpression.


OBJECTIVE
As both methods are known to be influenced by previous tissue processing, to analyse the applicability of both FISH and IHC to decalcified bone metastases of breast cancer.


METHODS
A tissue microarray (TMA) was constructed from 149 breast cancer bone metastases. Consecutive TMA sections were analysed by FISH (PathVysion) and IHC (HercepTest).


RESULTS
FISH analysis was interpretable in 113 (85.0%) cases. Amplification was seen in 14 (12.4%) interpretable metastases. HER-2 positivity on IHC analysis was 3+ in 9.8% of cases and 2+ in 11.3%. A comparison of the two techniques revealed high concordance. Of the 14 cases of amplification, 10 (71%) showed 3+ IHC staining, two (14%) showed 2+, one (7%) showed 1+, and one (7%) showed 0+. Three of the four amplified cases that did not show 3+ IHC staining had an equivocal FISH result, with a HER-2/centromere 17 ratio of 1.8-2.2. Of the 13 cases that showed IHC 3+ staining, amplification was present in 10 (77%).


CONCLUSIONS
HER-2 FISH analysis has an excellent success rate in highly standardised EDTA-decalcified bone metastases, suggesting that this method is easily applicable to decalcified tissues. The high concordance between IHC and FISH suggests that HER-2 IHC may be equally applicable to EDTA-treated tissues as to the usual formalin-fixed tissues.
Zustin
J
J
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. j.zustin@uke.uni-hamburg.de
Boddin
K
K
Tsourlakis
M C
MC
Burandt
E
E
Mirlacher
M
M
Jaenicke
F
F
Izbicki
J
J
Ruether
W
W
Rueger
J M
JM
Bokemeyer
C
C
Simon
R
R
Sauter
G
G
D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000737:chemistry* / Q000556:secondary*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D012680:Sensitivity and Specificity; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases