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HER-2/neu analysis in breast cancer bone metastases
  1. J Zustin1,
  2. K Boddin1,
  3. M C Tsourlakis1,
  4. E Burandt1,
  5. M Mirlacher1,
  6. F Jaenicke2,
  7. J Izbicki3,
  8. W Ruether4,
  9. J M Rueger5,
  10. C Bokemeyer6,
  11. R Simon1,
  12. G Sauter1
  1. 1
    Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany
  2. 2
    Department of Gynecology, University Medical Center Hamburg-Eppendorf, Germany
  3. 3
    Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Germany
  4. 4
    Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Germany
  5. 5
    Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Germany
  6. 6
    II. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Germany
  1. Dr J Zustin, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; j.zustin{at}uke.uni-hamburg.de

Abstract

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.

Aim: 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.

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Footnotes

  • Competing interests: None.