Expression of Inducible Nitric Oxide Synthase in Colorectal Cancer and Its Association with Prognosis

Abstract

Background: The expression of inducible nitric oxide synthase (iNOS) has been reported to be altered in a number of tumours, but its role in tumour biology is still unclear. Methods: iNOS was studied in a series of 157 colorectal carcinoma patients and its relation to tumour grade, stage, cell cycle regulators, cell proliferation as well as survival was assessed. Results: iNOS intensity was moderate or intense in 37% of the tumours. iNOS intensity and percentage of positive cells were higher in Dukes A and B tumours than in Dukes C and D tumours, and low iNOS expression intensity was related to high histological grade. iNOS expression correlated positively with cell cycle regulators p21 and AP-2. There was also a high iNOS expression intensity and high fraction of iNOS positive cells in tumours with a high amount of tumour infiltrating lymphocytes (TILs). The cancer related survival was significantly lower among patients with a low signal for iNOS and low iNOS percentage in tumour epithelium. In multivariate analysis iNOS was not an independent prognostic factor. Conclusions: These results suggest that iNOS has a protective role in colorectal carcinogenesis, but further studies are required to establish the clinical significance of iNOS in colorectal cancer.