Matrix metalloproteinase expression and outcome in patients with breast cancer: analysis of a published database.
Traditionally, matrix metalloproteinases (MMPs) have been implicated in cancer invasion and metastasis. Because of their role in these processes, several MMPs have been investigated for potential prognostic value as well as targets for antimetastatic therapy. In this investigation, we used a publically available database to relate messenger RNA expression levels for 17 different MMPs to tumor characteristics and outcome in patients with breast cancer. Of the MMPs investigated, only MMP-1 was significantly increased in tumors >2 cm in size compared with those <or=2 cm while MMP-1, -9, -12 and -15 were significantly elevated in high-grade compared with low-grade tumors. Only MMP-10 was higher in lymph node-positive compared with lymph node-negative cancers. Using univariate analysis, high expressions of MMP-1, -9, -12, -14 and -15 were associated with poor overall survival. Of these five, only MMP-14 predicted outcome independent of tumor size, tumor grade and lymph node status. None of the MMPs investigated were associated with good outcome. We conclude that only a minority of MMPs, i.e. MMP-1, -9, -12, -14 and -15, are associated with adverse outcome in patients with breast cancer. These MMPs are likely to be involved in mediating breast cancer progression and may thus be good targets for designing specific MMP inhibitors for the treatment of breast cancer.
McGowan
P M
PM
Department of Pathology and Laboratory Medicine, St Vincent's University Hospital, Dublin 4, Ireland.
Duffy
M J
MJ
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality* / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D003131:Combined Modality Therapy; D016001:Confidence Intervals; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015412:Mastectomy, Segmental; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011336:Probability; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D018714:Radiotherapy, Adjuvant; D012042:Registries; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D020782:Matrix Metalloproteinases