Overexpression of matrix-metalloproteinase-9 in human breast cancer: a potential favourable indicator in node-negative patients.
Matrix metalloprotease-9 (MMP-9; 92 kDa type IV collaganase, gelatinase B) is regarded as, important for degradation of the basement membrane and extracellular matrix during cancer invasion and other tissue-remodelling events. In this study we evaluate the prognostic value of MMP-9, by immunoperoxidase staining in a series of 210 breast cancer tissues. The results were quantitated using the HSCORE system, which consider both staining intensity and the percentage of cells stained at given intensities. MMP-9 status was compared with the concentration of cytosolic Cathepsin-D and with other established prognostic factors, in terms of disease free survival and overall survival. The median follow-up period was 62 months. MMP-9 staining was observed primarily in cancer cells, and to a lesser degree in surrounding stromal cells. MMP-9 expression was not detected in normal breast tissue. Levels of MMP-9 expression below the cut-off point were more frequently observed in larger (P = 0.014), invasive ductal histologic (P = 0.037), progesterone receptor (PR)-negative and PR-strong positive tumours (P< 0.001), as well as samples belonging to patients with stage III-IV disease (P = 0.009) and age 45-55 years (P = 0.011). In univariate analysis, node-negative breast cancer patients with tumors positive for MMP-9 had a considerable reduction in risk for relapse (RR = 0.45;P = 0.039) or death (RR = 0.32;P = 0.009). Multivariate analysis indicated that MMP-9 status was an independent favourable predictor of OS (RR = 0.47;P = 0.034) in node-negative but not in node-positive patients. Our results suggest that MMP-9 may be an independent favourable prognostic factor in node-negative breast cancer patients. The overexpression of MMP-9 in breast cancer may be also used as a marker to subdivide node negative breast cancer patients in order to determine the optimal treatment modality.
Scorilas
A
A
'G.Papanikolaou', Research Center of Oncology, Athens, Greece.
Karameris
A
A
Arnogiannaki
N
N
Ardavanis
A
A
Bassilopoulos
P
P
Trangas
T
T
Talieri
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008197:Lymph Node Excision; D008408:Mastectomy; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000096:biosynthesis*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010347:Patient Care Planning; D011379:Prognosis; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D020780:Matrix Metalloproteinase 9