Inducible nitric oxide synthase (iNOS) expression and its prognostic valuein prostate cancer

Objectives: The expression of inducible nitric oxide synthase (iNOS) was ev aluated in prostate cancer and the results were compared with other prognos tic factors and patients outcome. Materials and Methods: Clinical and histo pathological data and follow-tip information of 198 prostate cancer (PC) pa tients treated between the years 1973 and 1992 at Kuopio University Hospita l, Finland were collected from patient files. Archival tumor specimens were used for immunohistochemical analysis of iNOS. The expression of iNOS was analysed by light microscopy and the expression was scored into 3 grades (n egative weak or strong). Results: iNOS was expressed in tumor cells and in inflammatory cells inside and around the tumor. Normal and hyperplastic pro state tissues adjacent to tumors were negative or weakly positive for iNOS. The strong iNOS expression in tumor cells was related to high T-classifica tion (p = 0.001), metastasis (p = 0.06), high Gleason score (p = 0.0004), D NA aneuploidy (p = 0.0001) and perineural infiltration (p = 0.0001). iNOS e xpression was not linked with the density of tumor infiltrating lymphocytes or the expression of p53. The mean values of Ki-67, mitotic index and S-ph ase fraction were higher in tumors strongly expressing iNOS. In univariate survival analysis/the strong expression of iNOS was a significant predictor of poor survival in the entire cohort (p = 0.0002) and in the MO patients (p = 0.008), but was not an independent predictor of survival in Cox's mult ivariate analysis. Conclusion: iNOS has been related to stimulative and sup pressive effects on cancer cell growth, but the prognostic value of iNOS ha s not been previously studied in PC Here we could demonstrate an associatio n between strong iNOS expression and rapid cancer cell proliferation rate, dedifferentiation and advanced stage cancer. The strong iNOS expression was a predictor of poor survival in univariate analysis, but was inferior to e stablished prognostic factors in multivariate analysis.