Does type II nitric oxide synthase expression correlate with cellular proliferation in oral squamous cell carcinoma and dysplasia?

Head Neck. 2001 Mar;23(3):217-22. doi: 10.1002/1097-0347(200103)23:3<217::aid-hed1021>3.0.co;2-#.

Abstract

Background: Nitric oxide (NO) has been implicated both in tumor progression and inhibition. This study investigated whether type II nitric oxide synthase (NOS2) expression correlated with cell proliferation in oral squamous cell carcinoma (OSCC) and dysplasia.

Methods: Paraffin-embedded tissue samples of normal oral mucosa, OSCC, and dysplasia were assessed immunohistochemically using monoclonal antibodies to NOS2 and Ki-67 antigen. We used Western blotting to confirm NOS2 antibody specificity and protein expression in select cases.

Results: NOS2 staining was increased in OSCC relative to normal oral mucosa, in which no expression was found. Both NOS2 expression and Ki-67 indices independently correlated with grade of dysplasia (p < .001) but not with the degree of tumor differentiation. A positive correlation was found between NOS2 expression and Ki-67 in cases of mild and moderate dysplasia (p < .001), but not in severe dysplasia and OSCC.

Conclusions: No correlation exists between Ki-67 and NOS2 expression in severe dysplasia and OSCC. The findings suggest that the level of NO produced by NOS2 is insufficient to affect cellular proliferation in these conditions. The mechanism of NOS2 activation and the consequences of its expression remain to be fully explained.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor
  • Blotting, Western
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / pathology*
  • Cell Division
  • Culture Techniques
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Mouth Mucosa / enzymology
  • Mouth Mucosa / pathology
  • Mouth Neoplasms / enzymology*
  • Mouth Neoplasms / pathology*
  • Nitric Oxide Synthase / analysis
  • Nitric Oxide Synthase / metabolism*
  • Reference Values
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • Nitric Oxide Synthase