Prognostic significance of cyclooxygenase-2 pathway and angiogenesis in head and neck squamous cell carcinoma

Hum Pathol. 2002 Jul;33(7):708-14. doi: 10.1053/hupa.2002.125376.


Prostaglandins play a critical role in tumor development and growth by regulating numerous biologic processes, including tumor angiogenesis, with clear prognostic and therapeutic implications. The aim of this study was to investigate the prognostic relevance of cyclooxygenase-2 (COX-2) pathway activation in head and neck squamous cell carcinoma (HNSCC). COX-2 activity was analyzed in 52 consecutive patients by assessing protein expression and prostaglandin E(2) (PgE(2)) levels and was then correlated to vascular endothelial growth factor (VEGF) expression and tumor angiogenesis. We evaluated the prognostic impact of these parameters by Kaplan-Meier and Cox survival analysis. COX-2 expression by tumor cells was closely correlated to VEGF expression and to tumor vascularization. According to Kaplan-Meier analysis, patients with COX-2 tumor overexpression and with higher PgE(2) tumor levels had significantly shorter overall survival estimates (P = 0.022 and P = 0.033, respectively). Analogously, patients with more-vascularized tumors had worse survival than those with less-vascularized cancers (P = 0.032). Cox multivariate analysis demonstrated that the most significant prognostic factors were presence of lymph node metastasis, tumor vascularization, COX-2 protein expression, and PgE(2) tumor levels. This study demonstrates a close correlation between COX-2 pathway, VEGF expression, and tumor angiogenesis in HNSCC. In addition, COX-2 overexpression and higher tumor vascularization appear to predict a shorter survival in patients with head and neck cancer.

MeSH terms

  • Aged
  • Carcinoma, Squamous Cell / blood supply*
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / secondary
  • Cyclooxygenase 2
  • Dinoprostone / metabolism
  • Disease-Free Survival
  • Endothelial Growth Factors / metabolism
  • Female
  • Head and Neck Neoplasms / blood supply*
  • Head and Neck Neoplasms / enzymology*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Immunohistochemistry
  • Isoenzymes / metabolism*
  • Lymphokines / metabolism
  • Male
  • Membrane Proteins
  • Middle Aged
  • Neoplasm Staging
  • Neovascularization, Pathologic / enzymology*
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Isoenzymes
  • Lymphokines
  • Membrane Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone