Significant Relationship of Matrix Metalloproteinase 9 with Nuclear Grade and Prognostic Impact of Tissue Inhibitor of Metalloproteinase 2 for Incidental Clear Cell Renal Cell Carcinoma

ObjectiveTo examine the immunoreactivity of tumors for matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1, TIMP-2), and membrane type MMP 1 (MT-MMP-1), to evaluate the optimum assessment of incidental renal cell carcinoma.MethodsTumor samples from 120 incidental clear cell renal cell carcinoma (ICRCC) patients without distant metastasis or invasion beyond Gerota’s fascia were obtained by surgery. They were immunohistochemically stained for MMP-2, MMP-9, TIMP-1, TIMP-2, and MT-MMP-1. Immunoreactivity for these factors was analyzed by semiquantitative multivariate analysis for cancer-specific survival.ResultsThe cancer-specific 5 and 10-year survival rates were 91.4% and 91.4%, respectively. Univariate analysis revealed that nuclear grade (P = 0.0064) and TIMP-2 (P = 0.034) were significant prognostic factors. Matrix metalloproteinase 9 has a significant relationship with high nuclear grade RCC (P = 0.017) and was found to be an independent prognosticator by Cox multiple regression analysis (P = 0.0028).ConclusionsNuclear grade and TIMP-2 were significant prognostic factors of ICRCC. Multivariate analysis showed that a nuclear grade greater than 3 was associated with a 566% significant increase in the odds of cancer death. Strong expression of MMP-9 was associated with a 774% increase in the odds of high nuclear grade, with statistical significance. Although ICRCC is well known for having a favorable prognosis, patients with tumors having a high nuclear grade and strongly expressed MMP-9 and TIMP-2 should undergo strict postoperative follow-up.