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.

ABSTRACT

OBJECTIVE: To 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. METHODS: Tumor 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. RESULTS: The 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). CONCLUSIONS: Nuclear 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.