Activated matrix metalloproteinase-2--a potential marker of prognosis for epithelial ovarian cancer.
OBJECTIVE
To investigate the relationship between the expression of matrix metalloproteinase-2 (MMP-2) and clinical characteristics in patients with epithelial ovarian tumors, we examined the expression of MMP-2 in 26 epithelial benign ovarian tumors (EBOT) and 41 epithelial ovarian carcinomas (EOC) using semi-quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. We also analyzed pro-MMP-2 and activated MMP-2 in epithelial ovarian tumors using Western blot. RESULTS The expression levels of MMP-2 mRNA and overall protein were higher in EOC than in EBOT, but the differences were not statistically significant (P > 0.05). MMP-2 mRNA and immunoreactive protein for MMP-2 were not significantly associated with clinicopathological features in EOC. The positive percentages of the active form of MMP-2 were 71% in EOC and 42% in EBOT, respectively (P < 0.05). The positive percentage of the active form of MMP-2 in stage III and IV EOC was significantly higher (81%) than that (33%) in stage I and II EOC (P = 0.01). The expression of activated MMP-2 was significantly related to disease progression in EOC (P = 0.02). The percentages of active MMP-2 in positive immunoreaction tumor cells and fibroblasts were, respectively, 96 and 89%. The difference was not statistically significant (P = 0.54). The positive and negative predictive values of active MMP-2 for disease progression were 65 (19/29) and 75% (9/12), respectively, and the accuracy was 68% (28/41).


CONCLUSIONS
MMP-2 generally appears in epithelial ovarian tumors and there is a tendency to express more MMP-2, and especially activated MMP-2, in EOC. MMP-2 mRNA and pro-MMP-2 are not associated with the clinicopathological features in patients with EOC. There was a significant relationship between activated MMP-2 and invasiveness, metastasis, and disease progression in EOC and activated MMP-2 is a potential marker of prognosis.
Wu
Xiaohua
X
Department of Obstetrics and Gynecology, Fourth Affilaited Hospital, Hebei Medical University, Shijiazhuang, Hebei, 050011, People's Republic of China. xiaohuawu65@yahoo.com
Li
Haili
H
Kang
Lin
L
Li
Li
L
Wang
Weiping
W
Shan
Baoen
B
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D018093:Gelatinases / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D004792:Enzyme Precursors; D012333:RNA, Messenger; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase; D020778:Matrix Metalloproteinase 2