Coordinated upregulation of COX-2 and NF-kappaB is a steady feature of laryngeal carcinogenesis

ORL J Otorhinolaryngol Relat Spec. 2007;69(3):181-9. doi: 10.1159/000099229. Epub 2007 Jan 30.

Abstract

Background/aims: Laryngeal cancer is the endpoint of a multistage process involving hyperplastic and dysplastic lesions, not adequately defined in their molecular aspect. Our objective was to evaluate the expression of the prostaglandin-synthesizing enzyme cyclooxygenase-2 (COX-2) and the chief transcription factor nuclear factor-kappaB (NF-kappaB) in laryngeal carcinomas and their precursors, as well as to explore any association between the two molecules.

Methods: We performed paraffin section immunohistochemistry for COX-2 and the p65 subunit of NF-kappaB, in tissues from 129 patients with tumors or premalignancies. p65 cytoplasmic and nuclear immunostaining were listed individually.

Results: COX-2 was positively correlated with histopathological grading from normal mucosa to carcinomas (Spearman's coefficient r(s) = 0.286, p < 0.001). No association was revealed between COX-2 expression and tumor grade. p65 immunoreactivity, both of cytoplasmic and nuclear origin, increased along the carcinogenesis course, manifesting highest expression in invasive cancer (r(s) = 0.419, p < 0.001 and r(s) = 0.241, p < 0.001, respectively). Again, tumor grade had no influence on expression. COX-2 and p65 cytoplasmic, but no nuclear, expression showed a positive correlation (r(s) = 0.352, p < 0.001).

Conclusions: This study demonstrates that lesional advance in the larynx towards cancer is marked by ongoing upregulation of COX-2 and NF-kappaB. Synchronism between individual expressions may denote a regulatory role of the latter in COX-2 transactivation.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cyclooxygenase 2 / genetics*
  • Cyclooxygenase 2 / metabolism*
  • Disease Progression
  • Female
  • Humans
  • Hyperplasia / genetics
  • Hyperplasia / metabolism
  • Hyperplasia / pathology
  • Immunohistochemistry
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / metabolism*
  • Laryngeal Neoplasms / pathology
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Middle Aged
  • NF-kappa B p50 Subunit / genetics*
  • NF-kappa B p50 Subunit / metabolism*
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / metabolism*
  • Precancerous Conditions / pathology
  • Up-Regulation / genetics*

Substances

  • Membrane Proteins
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • Cyclooxygenase 2
  • PTGS2 protein, human