81 Citazioni (Scopus)

Abstract

Epidermal growth factor receptor (EGFR) overexpression is an unfavorable prognostic marker in laryngeal squamous cell carcinoma (SCC). EGFR stimulates cyclooxygenase-2 (COX-2) expression in normal human keratinocytes and squamous carcinoma cells. Based on these observations a prognostic role of COX-2 expression in laryngeal SCC can be hypothesized. Consequently, COX-2 expression was studied in laryngeal SCC (median follow-up = 47 months; range: 2-87 months) by quantitative immunohistochemistry (n = 61) and EGFR by binding assay (n = 51). Well-differentiated regions of laryngeal SCC revealed strong COX-2 immunostaining, whereas histologically normal areas neighboring tumor as well as poorly-differentiated tumors were negative. Immunohistochemical results were confirmed by Western blot analyses. Cox's regression analysis showed that the combination of low levels of COX-2 integrated density and high levels of EGFR covariates provided strong prediction, at 5-year follow-up, of both poor overall survival (chi(2) = 12.905; p = 0.0016) and relapse-free survival (chi(2) = 9.209; p = 0.01). In vitro studies on CO-K3 cell line, obtained from an EGFR positive, COX-2 negative poorly-differentiated laryngeal SCC, revealed that EGF stimulation failed to induce COX-2 expression and PGE2 production suggesting a change in EGFR signaling pathway. These findings indicate that COX-2 is overexpressed in less aggressive, low grade laryngeal SCC, whereas its expression is lost when tumors progress to a more malignant phenotype.
Lingua originaleEnglish
pagine (da-a)343-349
Numero di pagine7
RivistaInternational Journal of Cancer
Volume95
Stato di pubblicazionePubblicato - 2001

Keywords

  • Aged
  • Blotting, Western
  • Carcinoma, Squamous Cell
  • Cell Differentiation
  • Cell Line
  • Cyclooxygenase 2
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Isoenzymes
  • Keratinocytes
  • Kinetics
  • Laryngeal Neoplasms
  • Membrane Proteins
  • Middle Aged
  • Multivariate Analysis
  • Phenotype
  • Prognosis
  • Prostaglandin-Endoperoxide Synthases
  • Protein Binding
  • Receptor, Epidermal Growth Factor
  • Signal Transduction
  • Time Factors
  • Tumor Cells, Cultured
  • Up-Regulation

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