Inducible nitric oxide synthase and bcl-2 expression in nasopharyngeal cancer: Correlation with outcome of patients after radiotherapy

Abstract

Purpose: The expression of inducible nitric oxide synthase (iNOS) and bcl-2 proteins was evaluated and the prognostic significance determined in nasopharyngeal cancer (NPC) patients treated by radiotherapy. Methods and Materials: Tissue sections from 55 patients with NPC were assessed for iNOS and bcl-2 protein expression by immunohistochemistry, immunoelectron microscopy, and in situ hybridization before treatment. The markers were correlated with apoptosis (detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay) and clinicopathologic parameters. Results: All NPC sections exhibited positive iNOS and bcl-2 immunoreactivity, with a mean percentage of 6.24% ± 0.58% and 17.09% ± 2.48%, respectively. A significant positive correlation was observed between iNOS expression and the apoptotic index (p < 0.0001, Pearson's r = 0.8518), and bcl-2 expression correlated inversely with apoptosis (p = 0.0001; Pearson's r = -0.6170). A significant inverse correlation was found between iNOS and bcl-2 immunoreactivity (p < 0.0001, Pearson's r = -0.7144). Bcl-2 but not iNOS expression was associated with the stage of the tumor according to the criteria of the American Joint Committee on Cancer (1997) (p < 0.0001). Patients who had recurrence of the tumor and metastasis after radiotherapy had a lower expression of iNOS (p = 0.014 and p = 0.035, respectively), although overall survival was not significantly different statistically. Higher bcl-2 expression was also associated with local tumor recurrence (p = 0.005) but not with metastasis or overall survival. Conclusion: It appears that iNOS and bcl-2 expression may be potentially useful biomarkers for predicting the outcome of radiotherapy in NPC patients.