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.