ADAM-17 predicts adverse outcome in patients with breast cancer.
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.
McGowan
P M
PM
Department of Pathology, Laboratory Medicine, Conway Institute, University College Dublin, Dublin 4, Ireland.
McKiernan
E
E
Bolster
F
F
Ryan
B M
BM
Hill
A D K
AD
McDermott
E W
EW
Evoy
D
D
O'Higgins
N
N
Crown
J
J
Duffy
M J
MJ
D051722:ADAM Proteins / Q000096:biosynthesis*; D000072198:ADAM17 Protein; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis
D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human