Expression of MMP-2, -7, -9, MT1-MMP and TIMP-1 and -2 has no prognostic             relevance in patients with advanced epithelial ovarian cancer.
Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in tumor invasion, but their prognostic significance is still under discussion. We set out to analyze the epithelial and stromal expression of MMP-2, MMP-7, MMP-9, MT1-MMP, TIMP-1 and TIMP-2 in advanced epithelial ovarian cancers and to assess their prognostic value. A tissue microarray of malignant ovarian tumors from 69 patients was constructed. Immunostaining results were scored using the HSCORE and assessed by univariate analysis with Bonferroni correction and classical multidimensional scaling (CMDS). Kaplan-Meier survival curves calculated with regard to patient and tumor characteristics were compared by the log-rank test. Patients treated by primary surgery (n=43) had a higher tumor size and a trend toward higher epithelial MMP and TIMP expression than those treated by interval surgery (n=26). Optimal cytoreduction (residue ≤ 1 cm) was obtained in 27 and 18 patients, respectively. Clinical and histological characteristics were not different in patients with optimal cytoreduction and those with suboptimal cytoreduction. The expression of epithelial MMP-9 (P=0.002) and TIMP-2 (P=0.026) were higher in the latter group. CMDS failed to demonstrate any influence of MMP and TIMP expression with regard to cytoreduction outcome. MMP and TIMP expression did not influence survival. Their prognostic values were outweighed by histological type, lymph node involvement and cytoreduction. Standard statistical analysis adjusted after Bonferroni correction and CMDS reduced the relevance of MMPs and TIMPs in the prognosis of patients with advanced ovarian cancer.
Department of Obstetrics, Hôpital Tenon, AP-HP, F-75571 Paris, France. jean-luc.brun@chu-bordeaux.fr
Jean-Luc
JL
Brun
Annie
A
Cortez
Bénédicte
B
Lesieur
Serge
S
Uzan
Roman
R
Rouzier
Emile
E
Daraï
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D000077216:Carcinoma, Ovarian Epithelial; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D053511:Matrix Metalloproteinase 14 / Q000032:analysis*; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D020783:Matrix Metalloproteinase 7 / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009375:Neoplasms, Glandular and Epithelial / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D010052:Ovariectomy; D010297:Paris; D025341:Principal Component Analysis; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis*; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14