The prognostic value of the hypoxia markers CA IX and GLUT 1 and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy +/- chemotherapy

BMC Cancer. 2005 Apr 25:5:42. doi: 10.1186/1471-2407-5-42.


Background: Several parameters of the tumor microenvironment, such as hypoxia, inflammation and angiogenesis, play a critical role in tumor aggressiveness and treatment response. A major question remains if these markers can be used to stratify patients to certain treatment protocols. The purpose of this study was to investigate the inter-relationship and the prognostic significance of several biological and clinicopathological parameters in patients with head and neck squamous cell carcinoma (HNSCC) treated by radiotherapy +/- chemotherapy.

Methods: We used two subgroups of a retrospective series for which CT-determined tumoral perfusion correlated with local control. In the first subgroup (n = 67), immunohistochemistry for carbonic anhydrase IX (CA IX) and glucose transporter-1 (GLUT-1) was performed on the pretreatment tumor biopsy. In the second subgroup (n = 34), enzyme linked immunosorbent assay (ELISA) was used to determine pretreatment levels of the cytokines vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in serum. Correlation was investigated between tumoral perfusion and each of these biological markers, as well as between the markers mutually. The prognostic value of these microenvironmental parameters was also evaluated.

Results: For CA IX and GLUT-1, the combined assessment of patients with both markers expressed above the median showed an independent correlation with local control (p = 0.02) and disease-free survival (p = 0.04) with a trend for regional control (p = 0.06). In the second subgroup, IL-6 pretreatment serum level above the median was the only independent predictor of local control (p = 0.009), disease-free survival (p = 0.02) and overall survival (p = 0.005).

Conclusion: To our knowledge, we are the first to report a link in HNSCC between IL-6 pretreatment serum levels and radioresistance in vivo. This link is supported by the strong prognostic association of pretreatment IL-6 with local control, known to be the most important parameter to judge radiotherapy responses. Furthermore, the combined assessment of CA IX and GLUT-1 correlated independently with prognosis. This is a valuable indication that a combined approach is important in the investigation of prognostic markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / blood*
  • Biomarkers, Tumor*
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / blood*
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / radiotherapy
  • Disease-Free Survival
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation, Neoplastic*
  • Glucose Transporter Type 1 / blood*
  • Head and Neck Neoplasms / diagnosis*
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / radiotherapy
  • Humans
  • Immunohistochemistry
  • Interleukin-6 / blood*
  • Multivariate Analysis
  • Perfusion
  • Prognosis
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / blood*


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Glucose Transporter Type 1
  • Interleukin-6
  • Vascular Endothelial Growth Factor A
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases