title: Immunoreactivity for TIMP-2 is associated with a favorable prognosis in endometrial carcinoma.
abstract: Tissue inhibitors of metalloproteinases are important regulators of metalloproteinase activity, and the balance of active enzyme and inhibitor is a critical determinant of tumor cell invasiveness. This study aimed to evaluate the prognostic and clinical implications of the two main inhibitors of matrix metalloproteinases, TIMP-1 and TIMP-2, in endometrial carcinoma. The material consisted of 241 patients with primary endometrial carcinoma. The median follow-up time was 77 months. Expressions of TIMP-1 and TIMP-2 proteins were examined in paraffin-embedded tumor sections by immunohistochemical methods. Positive staining for TIMP-1 and -2 was observed in 88% and 86% of the primary tumors, respectively. The Kaplan-Meier analysis showed that the 5-year cancer-specific survival rate of the patients with TIMP-2 positive immunostaining was 89% and that of the TIMP-2 negative patients 78%. Positive immunoreaction for TIMP-2 correlated with favorable cancer-specific and overall survival. When including only endometrioid adenocarcinomas, a similar trend towards favorable survival was seen. Excluding stage IA carcinomas, the difference became again statistically significant. For TIMP-1, there was no statistically significant association with overall or cancer-specific survival. The Cox regression analysis showed stage, grade and TIMP-2 to be significant predictors of survival. We suggest that TIMP-2 may have a more important role in endometrial carcinoma progression than TIMP-1 and might serve as a potential marker for favorable prognosis in this type of cancer.
authors.affiliation: Department of Obstetrics and Gynecology, University of Oulu, PO Box 5000, 90014 Oulu, Finland. mhonkavu@paju.oulu.fi
authors.forename: Maria
authors.initials: M
authors.lastname: Honkavuori-Toivola
authors.forename: Anne
authors.initials: A
authors.lastname: Talvensaari-Mattila
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
authors.forename: Taina
authors.initials: T
authors.lastname: Turpeenniemi-Hujanen
authors.forename: Markku
authors.initials: M
authors.lastname: Santala
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods* / Q000706:statistics & numerical data; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2