Hypoxia-inducible factors HIF-1alpha and HIF-2alpha in head and neck cancer: relationship to tumor biology and treatment outcome in surgically resected patients

Cancer Res. 2002 May 1;62(9):2493-7.

Abstract

Hypoxia within head and neck squamous cell carcinoma (HNSCC) predicts a poor response to radiotherapy and poor prognosis. Hypoxia-inducible factor (HIF)-1 and HIF-2 are nuclear transcription factors that regulate the cellular response to hypoxia and are important for solid tumor growth and survival. Overexpression of HIF-1alpha and HIF-2alpha was demonstrated in three HNSCC cell lines under hypoxia and tumor tissue versus normal tissue (n = 20, HIF-1alpha, P = 0.023; HIF-2alpha, P = 0.013). On immunostaining, HIF-1alpha and HIF-2alpha expression were localized to tumor nuclei; HIF-2alpha expression was also seen in tumor-associated macrophages. Expression of HIF-1alpha in surgically treated patients with HNSCC (n = 79) was associated with improved disease-free survival (P = 0.016) and overall survival (P = 0.027).

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Basic Helix-Loop-Helix Transcription Factors
  • Carcinoma, Squamous Cell / blood supply
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Disease-Free Survival
  • HeLa Cells
  • Head and Neck Neoplasms / blood supply
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / surgery
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Immunohistochemistry
  • L-Lactate Dehydrogenase / metabolism
  • Middle Aged
  • Necrosis
  • Survival Rate
  • Trans-Activators / biosynthesis*
  • Transcription Factors / biosynthesis*
  • Treatment Outcome

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Trans-Activators
  • Transcription Factors
  • endothelial PAS domain-containing protein 1
  • L-Lactate Dehydrogenase