Patterns and levels of hypoxia in head and neck squamous cell carcinomas and their relationship to patient outcome.
OBJECTIVE
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
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 (< or =0.1% oxygen) had a shorter event-free survival time than patients with pO(2) 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 pO(2) and provide support for the development of noninvasive hypoxia positron emission tomographic studies with fluorine 18-labeled EF5.
Evans
Sydney M
SM
Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6072, USA. sydevans@mail.med.upen.edu
Du
Kevin L
KL
Chalian
Ara A
AA
Mick
Rosemarie
R
Zhang
Paul J
PJ
Hahn
Stephen M
SM
Quon
Harry
H
Lustig
Robert
R
Weinstein
Gregory S
GS
Koch
Cameron J
CJ
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia; D017341:Etanidazole / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000378:metabolism*; D007202:Indicators and Reagents / Q000378:metabolism*; D007822:Laryngeal Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology; D009959:Oropharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D005466:Fluorocarbons
D017341:Etanidazole; D006845:Hydrocarbons, Fluorinated; D007202:Indicators and Reagents; C096011:2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide; D005466:Fluorocarbons