Article
Chromosome 1 and 7 changes in HPV positive and negative tonsillar squamous cell carcinoma
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Published: | April 17, 2009 |
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Introductrion: Tonsillar squamous cell carcinoma (TSCC) is frequently associated with human papillomavirus (HPV). Chromosomal alterations are often observed. The aim of this study was to assess chromosome 1 and 7 copy number changes in relation to HPV-presence and prognosis of TSCC.
Methods: 70 TSCC with known clinical outcome and cell cycle protein expression profiles, and of which 36% showed HPV16-integration, were analyzed by Fluorescence In Situ Hybridization using chromosome 1- and 7-specific centromere DNA probes.
Results: Disomy for chromosome 1 and 7 was present in 26/70 TSCC (37%) and strongly associated with HPV-presence (16/26; p=0.001). Aneusomies for both chromosomes were observed in the remaining TSCC of which 24 tumors showed balanced and 20 unbalanced copy numbers (19 cases with higher chromosome 7 copy numbers). Aneusomy correlated significantly with tobacco- and alcohol consumption (p=0.001 and p=0.007, respectively) and higher T-stage (p=0.03). Both HPV-positivity and chromosome disomy were significantly associated with a favorable prognosis (p=0.003 and p=0.011, respectively).
Conclusions: HPV-associated TSCC are genetically more stable than HPV-negative tumors, suggesting that HPV-integration preferentially occurs in (near) diploid lesions. HPV-positivity and chromosome disomy are favorable prognosticators, although less powerful than previously reported indicators, i.e. low tobacco consumption, low T-stage and p21CIP1/WAF1 overexpression.