OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVES: 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. METHODS: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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Sumanta Pal; Arun Azad; Shailender Bhatia; Harry Drabkin; Brian Costello; John Sarantopoulos; Ravindran Kanesvaran; Richard Lauer; Alexander Starodub; Ralph Hauke; Christopher J Sweeney; Noah M Hahn; Guru Sonpavde; Stephen Richey; Timothy Breen; Gabriel Kremmidiotis; Annabell Leske; Elizabeth Doolin; David C Bibby; Jeremy Simpson; Jose Iglesias; Thomas Hutson Journal: Clin Cancer Res Date: 2015-03-18 Impact factor: 12.531