Prognostic significance of matrix metalloproteinase-9 (MMP-9) in epithelial ovarian cancer.
OBJECTIVE
We investigated the expression of matrix metalloproteinase-9 (MMP-9) and its relation to clinicopathologic factors and survival and also to previously analyzed expressions of CD44 and hyaluronan in epithelial ovarian cancer.


METHODS
The expression of MMP-9 was analyzed immunohistochemically in 292 primary tumors and their 31 metastases.


RESULTS
A low proportion of strong MMP-9 expression in cancer cells and high stromal MMP-9 expression correlated with advanced stage of the tumor (p=0.003, p=0.02, respectively). Stromal MMP-9 expression significantly correlated with hyaluronan positivity (p<0.0005), whereas MMP-9 did not correlate with CD44. In univariate analysis, a longer 10-year disease-related survival (DRS) was found in patients with a high proportion of MMP-9 or strong MMP-9 expression in cancer cells (p=0.02, p=0.05, respectively). However, high stromal expression of MMP-9 indicated short DRS (p=0.01). In multivariate analysis of all patients, MMP-9 expressing cancer or stromal cells were not independent prognostic factors, while in FIGO stage I patients a high percentage of MMP-9 positive cancer cells was associated with long DRS (p=0.008).


CONCLUSIONS
These data suggest that MMP-9 has a dual role in tumor progression, acting against tumor advancement when in tumor epithelium and promoting tumor progression while in the stroma.
Sillanpää
S
S
Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Kuopio, and Department of Clinical Pathology, Kuopio University Hospital, Finland.
Anttila
M
M
Voutilainen
K
K
Ropponen
K
K
Turpeenniemi-Hujanen
T
T
Puistola
U
U
Tammi
R
R
Tammi
M
M
Sironen
R
R
Saarikoski
S
S
Kosma
V-M
VM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D006820:Hyaluronic Acid / Q000096:biosynthesis; D007150:Immunohistochemistry; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D011379:Prognosis; D016896:Treatment Outcome
C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D020780:Matrix Metalloproteinase 9