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

Abstract

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.

• Authors: Pastora Beardo, David Truan Cacho, Laura Izquierdo, Joan Bautista Alcover-Garcia, Antonio Alcaraz, Javier Extramiana, Carmen Mallofré
• Journal: Pathology oncology research : POR (Pathol Oncol Res) Vol. 25 Issue 1 Pg. 289-299 (Jan 2019) ISSN: 1532-2807 [Electronic] Switzerland
• PMID: 29103203 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• TIMP2 protein, human
• Tissue Inhibitor of Metalloproteinase-2
• MMP2 protein, human
• Matrix Metalloproteinase 2

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor
• Carcinoma, Renal Cell (metabolism, mortality, pathology, surgery)
• Disease Progression
• Female
• Follow-Up Studies
• Humans
• Kidney Neoplasms (metabolism, mortality, pathology, surgery)
• Male
• Matrix Metalloproteinase 2
• Middle Aged
• Nephrectomy (mortality)
• Prognosis
• Retrospective Studies
• Survival Rate
• Tissue Inhibitor of Metalloproteinase-2 (metabolism)