Patterns and Levels of Hypoxia in Head and Neck Squamous Cell Carcinomas and Their Relationship to Patient Outcome

Sydney M. Evans, Kevin L. Du, Ara A. Chalian, Rosemarie Mick, Paul J. Zhang, Stephen M. Hahn, Harry Quon, Robert Lustig, Gregory S. Weinstein, Cameron J. Koch

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Purpose: EF5, a 2-nitroimidazole hypoxia marker, was used to study the presence, levels, and prognostic significance of hypoxia in primary head and neck squamous cell tumors. Methods and Materials: Twenty-two patients with newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, or larynx with at least 2 years of clinical follow-up were included in this study. Quantitative analyses of EF5 immunofluorescence was carried out, and these data were compared with patient outcome. Results: EF5 immunostaining showed substantial intra- and intertumoral hypoxic heterogeneity. The majority of cells in all tumors were well oxygenated. Three patterns of EF5 binding in cells were identified using criteria based on the cellular region that was stained (peripheral or central) and the relationship of binding to necrosis. We tested the association between EF5-binding levels with event-free and overall survival irrespective of the pattern of cellular binding or treatment regimen. Patients with tumors containing EF5-binding regions corresponding to severe hypoxia (≤0.1% oxygen) had a shorter event-free survival time than patients with pO2 values greater than 0.1% (p = 0.032). Nodal status was also predictive for outcome. Conclusions: These data illustrate the potential utility of EF5 binding based on quantitative immunohistochemistry of tissue pO2 and provide support for the development of noninvasive hypoxia positron emission tomographic studies with fluorine 18-labeled EF5.

Original languageEnglish (US)
Pages (from-to)1024-1031
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number4
StatePublished - Nov 15 2007
Externally publishedYes


  • EF5
  • Head and neck cancer
  • Hypoxia
  • Nitroimidazole
  • Squamous cell carcinoma

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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