Genomic Maintenance & Repair

Monday, October 17, 2005 3:00 PM-5:00 PM Exhibit Hall

(PP297) The correlation between hypoxia and microsatellite alterations in head and neck squamous cell carcinoma.

De Schutter, Harlinde*,1, Barbé, Barbara1, Spaepen, Marijke2, Janssen, Hilde1, Haustermans, Karin1, Begg, Adrian3, Nuyts, Sandra1, 1 Department of Radiation Oncology, Leuven, Belgium, Belgium2 Centre for Human Genetics, Leuven, Belgium, Belgium3 Experimental Therapy, Amsterdam, The Netherlands, The Netherlands

ABSTRACT- Introduction: Like in other cancers, genomic instability in HNSCC (Head and Neck Squamous Cell Carcinoma) is partly induced by the tumoral micro-environment of which the presence of hypoxia is a significant pathofysiological characteristic. Genomic instability is, amongst others, characterized by MSI (microsatellite instability) and LOH (loss of heterozygosity). The aim of the project was to find out if there exists a correlation between MSI/LOH and hypoxia and to evaluate the predictive value of both parameters on outcome. Materials and methods: 27 patients with HNSCC treated by surgery were included so far. For the evaluation of hypoxia, we performed immunohistochemistry on paraffin embedded material, using pimonidazole as an extrinsic marker and CA IX (carbonic anhydrase IX), GLUT-1 (glucose transporter-1) and HIF-1 (hypoxia-inducible factor 1) as possible intrinsic markers. MSI and LOH were assessed by PCR with 14 fluorescent labeled microsatellite markers, organized in three multiplexes. These were evaluated by automatic fragmentanalysis. Results: We found LOH in 1 marker in 11.1% of all patients (3/27). LOH in two or more markers was found in 29.6% (8/27). MSI in 1 marker was found in 14.8% of all patients (4/27), while MSI in 2 or more markers was found in 7.4% (2/27). We found a correlation between pimonidazole and N-stage (p=0.020) and disease-stage (p=0.047), and between GLUT-1 and differentiation (p=0.013). We also found a significant correlation between LOH and N-stage (p=0.034) and disease-stage (p=0.044). Patients expressing either MSI or LOH had a poorer outcome than patients without these genomic alterations (p=NS). We did not see a correlation between hypoxia and outcome. Finally, patients with either MSI or LOH tended to have higher pimonidazole values (p=NS). Conclusion: We conclude that we could see a trend for a correlation between MSI/LOH and outcome, and between MSI/LOH and hypoxia. We will try to validate these findings in a larger patient group. These results will be presented at the time of the congress.

Key words: head and neck squamous cell carcinoma, hypoxia, microsatellite instability, loss of heterozygosity

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2005 RRS