HER-2/neu gene amplification by fluorescence in situ hybridization allows risk-group assessment in node-negative breast cancer.

  • Authors:
    • N Harbeck
    • J S Ross
    • S Yurdseven
    • P Dettmar
    • M Pölcher
    • W Kuhn
    • K Ulm
    • H Graeff
    • M Schmitt
  • View Affiliations

  • Published online on: April 1, 1999     https://doi.org/10.3892/ijo.14.4.663
  • Pages: 663-734
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Abstract

In a collective of 112 node-negative breast cancer patients, we compared the prognostic impact of HER-2/neu gene amplification (AMP) determined by fluorescence in situ hybridization (FISH) and HER-2/neu protein overexpression (EXP) measured by immunohistochemistry (IHC) with traditional prognostic factors (tumor size, grade, steroid hormone receptor status, menopausal status) and tumor invasion markers uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 determined by enzyme immunoassay (ELISA). Median follow-up in patients still alive at time of analysis was 7 years. Automated FISH and IHC were performed on parallel-cut formalin-fixed paraffin-embedded tissue sections. HER-2/neu AMP was detected by FISH in 31% and HER-2/neu EXP was measured by IHC in 41% of the cases. In 13% of the tumors, both AMP and EXP were found. FISH and IHC results were concordant in 56% of all analyzed cases. In univariate analysis, HER-2/neu AMP significantly predicted both disease-free (DFS) and overall survival (OS). HER-2/neu EXP was significant for OS, only. In multivariate analysis of all analyzed prognostic factors, HER-2/neu AMP was the only independent predictive factor for both DFS and OS. CART analysis revealed that HER-2/neu AMP together with the combination uPA/PAI-1 allowed optimal risk-group assessment after a 7-year median follow-up: patients with low levels of both uPA and PAI-1 and no HER-2/neu AMP had a significantly lower relapse rate (4.6%) than the remaining patients (32%). In conclusion, HER-2/neu gene AMP determined by FISH allowed a more accurate risk-group assessment than HER-2/neu protein EXP measured by IHC. Combining the HER-2/neu gene status measured by FISH with levels of tumor invasion markers uPA and PAI-1 improves clinically relevant risk-group assessment. In addition to its prognostic strength, the significant impact of HER-2/neu AMP on OS may reflect its ability to predict resistance to systemic therapy.

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Apr 1999
Volume 14 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Harbeck N, Ross J, Yurdseven S, Dettmar P, Pölcher M, Kuhn W, Ulm K, Graeff H and Schmitt M: HER-2/neu gene amplification by fluorescence in situ hybridization allows risk-group assessment in node-negative breast cancer.. Int J Oncol 14: 663-734, 1999
APA
Harbeck, N., Ross, J., Yurdseven, S., Dettmar, P., Pölcher, M., Kuhn, W. ... Schmitt, M. (1999). HER-2/neu gene amplification by fluorescence in situ hybridization allows risk-group assessment in node-negative breast cancer.. International Journal of Oncology, 14, 663-734. https://doi.org/10.3892/ijo.14.4.663
MLA
Harbeck, N., Ross, J., Yurdseven, S., Dettmar, P., Pölcher, M., Kuhn, W., Ulm, K., Graeff, H., Schmitt, M."HER-2/neu gene amplification by fluorescence in situ hybridization allows risk-group assessment in node-negative breast cancer.". International Journal of Oncology 14.4 (1999): 663-734.
Chicago
Harbeck, N., Ross, J., Yurdseven, S., Dettmar, P., Pölcher, M., Kuhn, W., Ulm, K., Graeff, H., Schmitt, M."HER-2/neu gene amplification by fluorescence in situ hybridization allows risk-group assessment in node-negative breast cancer.". International Journal of Oncology 14, no. 4 (1999): 663-734. https://doi.org/10.3892/ijo.14.4.663