Pathology & Oncology Research

, Volume 25, Issue 1, pp 289–299 | Cite as

Cancer-Specific Survival Stratification Derived from Tumor Expression of Tissue Inhibitor of Metalloproteinase-2 in Non-Metastatic Renal Cell Carcinoma

  • Pastora BeardoEmail author
  • David Truan Cacho
  • Laura Izquierdo
  • Joan Bautista Alcover-Garcia
  • Antonio Alcaraz
  • Javier Extramiana
  • Carmen Mallofré
Original Article


Degradation of the extracellular matrix is a prerequisite for the processes of cancer cell invasion and metastasis. The purpose of our study was to assess the association of matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-9) and their inhibitors (TIMP-1 and TIMP-2) with renal cell carcinoma (RCC) progression and cancer-specific survival (CSS), using immunohistochemical analysis of 60 formalin-fixed, paraffin-embedded sections of tumor tissue and normal tissue near the tumor from surgical T1-3bN0 M0 RCC specimens. Significant overexpression of MMP-2 in tumor and normal tissue was correlated with advanced stages, tumor size, sarcomatous differentiation and clinical symptoms. Overall survival was 31.7% (55.2% M0, 9.7% M1) and CSS 56.7% (100% M0, 16.1% M1) with a follow-up of 76 (5–230) months. Fuhrman grade [HR 2.87 (95% CI: 1.28–6.45); p = 0.01], tumor size [HR 1.13 (95% CI: 1.03–1.26); p = 0.009] and low TIMP-2 expression [HR 0.35 (95% CI: 0.16–0.78); p = 0.01] were independent predictive factors of CSS and stratified the patients into three groups with different rates of 10-year CSS; [100%, 73.9% and 20.5% for the good, intermediate and poor prognosis group respectively (p = 0.000006)] . This study offers strong evidence that TIMP-2 expression in tumor tissue may play a crucial role in progression and poor prognosis in human localized and locally advanced RCC.


Matrix metalloproteinases Tissue inhibitors of metalloproteinases Renal cell carcinoma, Metastasis, Survival 


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Copyright information

© Arányi Lajos Foundation 2017

Authors and Affiliations

  1. 1.Department of UrologyAraba University HospitalVitoria-GasteizSpain
  2. 2.Department of UrologyMarques de Valdecilla University HospitalSantanderSpain
  3. 3.Department of UrologyClínic HospitalBarcelonaSpain
  4. 4.Department of PathologyUniversitat Autonoma of Barcelona and Clinic HospitalBarcelonaSpain

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