No Detectable Hypoxia in Malignant Salivary Gland Tumors: Preliminary Results
Received 31 March 2008; received in revised form 23 June 2008; accepted 23 June 2008. published online 29 October 2008.
Purpose
Hypoxia is detected in most solid tumors and is associated with malignant progression and adverse treatment outcomes. However, the oxygenation status of malignant salivary gland tumors has not been previously studied. The aim of this study was to investigate the potential clinical relevance of hypoxia in this tumor type.
Methods and Materials
Twelve patients scheduled for surgical resection of a salivary gland tumor were preoperatively injected with the hypoxia marker pimonidazole and the proliferation marker iododeoxyuridine. Tissue samples of the dissected tumor were immunohistochemically stained for blood vessels, pimonidazole, carbonic anhydrase-IX, glucose transporters-1 and -3 (Glut-1, Glut-3), hypoxia-inducible factor-1α, iododeoxyuridine, and epidermal growth factor receptor. The tissue sections were quantitatively assessed by computerized image analysis.
Results
The tissue material from 8 patients was of sufficient quality for quantitative analysis. All tumors were negative for pimonidazole binding, as well as for carbonic anhydrase-IX, Glut-1, Glut-3, and hypoxia-inducible factor-1α. The vascular density was high, with a median value of 285 mm−2 (range, 209–546). The iododeoxyuridine-labeling index varied from <0.1% to 12.2% (median, 2.2%). Epidermal growth factor receptor expression levels were mostly moderate to high. In one-half of the cases, nuclear expression of epidermal growth factor receptor was observed.
Conclusion
The absence of detectable pimonidazole binding, as well as the lack of expression of hypoxia-associated proteins in all tumors, indicates that malignant salivary gland tumors are generally well oxygenated. It is unlikely that hypoxia is a relevant factor for their clinical behavior and treatment responsiveness.
∗Department of Otorhinolaryngology, Head and Neck Surgery, Deventer Hospital, Deventer, The Netherlands
†Department of Otorhinolaryngology, Head and Neck Surgery, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
‡Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
§Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Reprint requests to: J. H. A. M. Kaanders, M.D., Ph.D., Department of Radiation Oncology, 874, Radboud University Nijmegen Medical Centre, P.O. Box 9101, Nijmegen 6500 HB The Netherlands. Tel: (31) 243614515; Fax: (31) 243610792
Supported by Grant KUN 98-1814 from the Dutch Cancer Society.
ABSTRACT