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Annals of Oncology Advance Access published online on January 30, 2008
Annals of Oncology, doi:10.1093/annonc/mdm609
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© 2008 European Society for Medical Oncology. For Permissions, please email: journals.permissions@oxfordjournals.org

ADAM-17 predicts adverse outcome in patients with breast cancer

P. M. McGowan1,2, E. McKiernan1,2, F. Bolster1,2, B. M. Ryan1,2,3, A. D. K. Hill1,2, E. W. McDermott1,2, D. Evoy1,2, N. O'Higgins1,2, J. Crown4 and M. J. Duffy1,2,*

1 Department of Pathology, Laboratory Medicine
2 UCD School of Medicine and Medical Science, Conway Institute, University College Dublin, Dublin 4, Ireland
3 Cancer Prevention Fellowship Program, Office of Preventive Oncology, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
4 Medical Oncology, St Vincent's University Hospital, Dublin 4, Ireland

* Correspondence to: Prof. M. J. Duffy, Nuclear Medicine Laboratory, St Vincent's University Hospital, Dublin 4, Ireland. Tel: +353-1-2094378; Fax: +353-1-2696018; E-mail: michael.j.duffy{at}ucd.ie

ADAM-17 is a matrix metalloproteinase-like enzyme involved in the release of several ligands that have been shown to promote both cancer formation and progression. These ligands include transforming growth factor-{alpha}, amphiregulin, heparin-binding epidermal growth factor, epiregulin and tumor necrosis factor-{alpha}. In this investigation, we measured the expression of total ADAM-17 by enzyme-linked immunosorbent assay in 153 invasive breast cancers. We also measured the precursor and active forms by western blotting in 140 invasive breast cancers. Expression of ADAM-17 was significantly increased in high-grade compared with low-grade tumors and was independent of tumor size, lymph node metastasis and estrogen receptor status. Patients with high expression of ADAM-17 had a significantly shorter overall survival compared with those with low expression. Significantly, the prognostic impact of ADAM-17 was independent of conventional prognostic factors for breast cancer. Our results are further evidence that ADAM-17 is involved in breast cancer progression and thus provides further impetus for exploiting ADAM-17 as new target for cancer treatment.

ADAM-17, breast cancer, metalloproteinases, prognosis

Received for publication September 27, 2007. Revision received December 21, 2007. Accepted for publication December 24, 2007.


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