Prognostic significance of stromal metalloproteinase-2 in ovarian adenocarcinoma and its relation to carcinoma progression.
OBJECTIVE
MMP-2 expression in ovarian cancer cells has been correlated with poor prognosis. This study attempts to assess the prognostic importance of stromal MMP-2 in patients with ovarian endometrioid and serous adenocarcinoma.


METHODS
MMP-2, MMP-2 activator, MT1-MMP, and its inhibitor (TIMP-2) were immunostained in 84 primary epithelial ovarian carcinomas (EOCs) (35 endometrioid adenocarcinomas [ECs] and 49 serous adenocarcinomas [SCs]). Results were correlated to pathological subtypes, tumor stage, grade, size, and to recurrence-free and cancer-specific survival.


RESULTS
MMP-2 and stromal MMP-2 were detected in all carcinoma cells of 22.2% of EC and 77.8% of SC tumors. MT1-MMP co-localized with MMP-2. TIMP-2 staining was weak and cytoplasmically distributed in all tumors. Univariant analysis showed expression of stromal MMP-2 significantly associated with advanced stage (P = 0.018), higher grade (P = 0.005), serous subtype (P = 0.02), smaller tumor size at operation (P = 0.001), and higher incidence of recurrence (P = 0.042), but not with the rate of death due to cancer. By multiple Cox proportional hazard regression analysis, patient survival and disease-free survival were significantly related to the presence of stromal MMP-2 in EC but not SC patients (P < 0.05). However, after multivariant analysis, the associations with patient age, tumor stage, grade, and size no longer existed. In stepwise selection, tumor stage remained the most important predictor of patient survival and disease-free survival in ovarian EC and SC, but stromal MMP-2 remained the most important predictor of recurrence-free survival in patients with EC.


CONCLUSIONS
Stromal MMP-2 occurs early and may play a role early in EOC invasion. Tumor stage and stromal MMP-2 are important predictors of disease-free survival.
Torng
Pao-Ling
PL
Department of Obstetrics and Gynecology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. ctl@ha.mc.ntu.edu.tw
Mao
Tsui-Lien
TL
Chan
Wing-Yee
WY
Huang
Su-Cheng
SC
Lin
Chin-Tang
CT
D018269:Carcinoma, Endometrioid / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000096:biosynthesis; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D017154:Stromal Cells / Q000201:enzymology / Q000473:pathology; D015996:Survival Rate; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D016896:Treatment Outcome
D019716:Tissue Inhibitor of Metalloproteinase-2; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2