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

Int J Radiat Oncol Biol Phys. 2003 Jul 1;56(3):837-45. doi: 10.1016/s0360-3016(03)00122-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • In Situ Nick-End Labeling
  • Male
  • Microscopy, Immunoelectron
  • Middle Aged
  • Nasopharyngeal Neoplasms / chemistry*
  • Nasopharyngeal Neoplasms / radiotherapy
  • Neoplasm Proteins / analysis*
  • Nitric Oxide Synthase / analysis*
  • Nitric Oxide Synthase Type II
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / analysis*
  • Statistics as Topic

Substances

  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II