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Immunoreactivity for TIMP-2 is associated with a favorable prognosis in endometrial carcinoma

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Tumor Biology

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.

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Acknowledgments

We would like to thank Mrs. Anne Bisi for her skillful technical assistance during this work.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Oulu, PO Box 5000, 90014, Oulu, Finland

    Maria Honkavuori-Toivola, Anne Talvensaari-Mattila & Markku Santala

  2. Department of Pathology, University of Oulu, PO Box 5000, 90014, Oulu, Finland

    Ylermi Soini

  3. Department of Pathology and Forensic Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, School of Medicine, Cancer Center of Eastern Finland, University of Eastern Finland, PO Box 1627, 70211, Kuopio, Finland

    Ylermi Soini

  4. Department of Oncology and Radiotherapy, University of Oulu, PO Box 5000, 90014, Oulu, Finland

    Taina Turpeenniemi-Hujanen

Authors
  1. Maria Honkavuori-Toivola
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  2. Anne Talvensaari-Mattila
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  4. Taina Turpeenniemi-Hujanen
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Correspondence to Maria Honkavuori-Toivola.

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Honkavuori-Toivola, M., Talvensaari-Mattila, A., Soini, Y. et al. Immunoreactivity for TIMP-2 is associated with a favorable prognosis in endometrial carcinoma. Tumor Biol. 33, 935–941 (2012). https://doi.org/10.1007/s13277-012-0321-7

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  • DOI: https://doi.org/10.1007/s13277-012-0321-7

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