Strong significant correlation between MMP-9 and systemic symptoms in patients with localized renal cell carcinoma

To identify a relationship between clinical symptoms and matrix metalloproteinase (MMP)-2 and MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, and membrane type MMP-1.

Tumor samples from 232 patients with renal cell carcinoma with no distant metastasis were immunohistochemically stained for MMP-2 and MMP-9, TIMP-1 and TIMP-2, and membrane type MMP-1. The immunoreactivity of these factors was analyzed by semiquantitative multivariate analysis for correlation with clinical symptoms.

Patard's criteria were used to classify symptoms at initial tumor clinical presentation, with three groups defined: S1, S2, and S3. The cancer-specific 5-year survival rate was 88.7%, 74.7%, and 67.6% for S1 (145 patients), S2 (69 patients), and S3 (18 patients), respectively (P = 0.0015). Multiple logistic regression analysis of preference was used to determine whether differences in the contribution of the symptoms were statistically significant. A maximal tumor diameter of 40 mm or greater and positive venous invasion were associated with a 262% and 281% increase in the odds of local symptoms, respectively. MMP-9 positive cases were associated with a 2979% increase in the odds of systemic symptoms with significance.

This study found a strong significant correlation between the histopathologic expression of MMP-9 and the systemic symptoms of renal cell carcinoma. We propose the histopathologic measurement of MMP-9 as a useful tool for assessing the prognosis of patients with renal cell carcinoma with systemic symptoms.