Silke Wemmert1, Maximilian Linxweiler2, Cornelia Lerner2, Florian Bochen2, Philipp Kulas2, Johannes Linxweiler3, Sigrun Smola4, Steffi Urbschat5, Stefan Wagenpfeil6, Bernhard Schick2. 1. Department of Otorhinolaryngology, Saarland University Medical Center, Kirrberger Street 100, 66421, Homburg (Saar), Germany. silke.wemmert@uks.eu. 2. Department of Otorhinolaryngology, Saarland University Medical Center, Kirrberger Street 100, 66421, Homburg (Saar), Germany. 3. Department of Urology, Saarland University, Homburg (Saar), Germany. 4. Institute of Virology, Saarland University Medical Center, Homburg (Saar), Germany. 5. Department of Neurosurgery, Saarland University, Homburg (Saar), Germany. 6. Institute for Medical Biometry, Epidemiology and Medical Informatics, Saarland University, Homburg (Saar), Germany.
Abstract
PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is one of the most common human cancer types with a very poor prognosis despite improvements in therapeutic modalities. The major known risk factors are tobacco use and alcohol consumption or infection with high-risk human papilloma viruses (HPV), especially in oropharyngeal tumors. The current management based on the assessment of a variety of clinical and pathological parameters does not sufficiently predict outcome. METHODS: Chromosomal alterations detected in HNSCCs were characterized by metaphase comparative genomic hybridization (CGH) and correlated with clinical parameters as well as survival time. Candidate regions were validated by quantitative polymerase chain reaction, fluorescence-in situ-hybridization (FISH) on dapped tumor tissue and liquid-based cytological smear preparations. In addition, HPV status was determined by polymerase chain reaction and simultaneous immunocytochemical p16INK4a-Ki67 staining. RESULTS: The most frequent DNA copy number gains were observed on chromosome arms 3q, 8q, 5p, 7q, 12p, and 12q. DNA copy number decreases occurred most frequently at 3p, 17p, 4q, and 5q. FISH analysis verified in part the observed alterations by CGH on dapped tissues and was especially able to detect the most frequent DNA copy changes in cytological specimens. CONCLUSION: The combination of HPV status and prognostic copy number alteration detected by FISH in biopsies or cytological specimens may be an applicable protocol for screening head and neck cancer patients prior to therapy.
PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is one of the most common humancancer types with a very poor prognosis despite improvements in therapeutic modalities. The major known risk factors are tobacco use and alcoholconsumption or infection with high-risk humanpapilloma viruses (HPV), especially in oropharyngeal tumors. The current management based on the assessment of a variety of clinical and pathological parameters does not sufficiently predict outcome. METHODS: Chromosomal alterations detected in HNSCCs were characterized by metaphase comparative genomic hybridization (CGH) and correlated with clinical parameters as well as survival time. Candidate regions were validated by quantitative polymerase chain reaction, fluorescence-in situ-hybridization (FISH) on dapped tumor tissue and liquid-based cytological smear preparations. In addition, HPV status was determined by polymerase chain reaction and simultaneous immunocytochemical p16INK4a-Ki67 staining. RESULTS: The most frequent DNA copy number gains were observed on chromosome arms 3q, 8q, 5p, 7q, 12p, and 12q. DNA copy number decreases occurred most frequently at 3p, 17p, 4q, and 5q. FISH analysis verified in part the observed alterations by CGH on dapped tissues and was especially able to detect the most frequent DNA copy changes in cytological specimens. CONCLUSION: The combination of HPV status and prognostic copy number alteration detected by FISH in biopsies or cytological specimens may be an applicable protocol for screening head and neck cancerpatients prior to therapy.
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