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Enhanced apoptosis correlates with poor survival in patients with laryngeal cancer but not with cell proliferation,bcl-2 or p53 expression
Institution:1. Departments of Oncology, Tampere University Hospital, PO Box 2000, FIN-33521 Tampere, Finland;2. Pathology and Forensic Medicine, Tampere University Hospital, PO Box 2000, FIN-33521 Tampere, FinlandOtorhinolaryngology;4. Medical Library, University of Kuopio and Kuopio University Hospital, Kuopio, Finland;5. Computer Centre, University of Kuopio and Kuopio University Hospital, Kuopio, Finland;1. Department of Materials Science & Engineering, Iowa State University, Ames, IA 50011, USA;2. Department of Chemical & Biological Engineering, Iowa State University, Ames, IA 50011, USA;3. Ames National Laboratory, Ames, IA 50011, USA;1. Research Institute for Integrated Management of Coastal Areas, Universitat Politècnica de València, Paranimf 1, 46730, Grao de Gandía, Valencia, Spain;2. Department of Analytical Chemistry, Universitat de València, Dr. Moliner 50, 46100, Burjassot, Valencia, Spain;3. Department of Structural and Molecular Biology, Division of Biosciences, Darwin Building, University College London, Gower Street, London WC1E 6BT, United Kingdom;5. Department of Biochemical Engineering, Division of Engineering, Roberts Building, University College London, Gower Street, London WC1E 6BT, United Kingdom;4. ISIS Facility, Science and Technology Facilities Council, Rutherford Appleton Laboratory, Harwell Oxford, Didcot OX11 0QX, United Kingdom;1. Department of Marine Chemistry, Faculty of Marine Science, Chabahar Maritime University, Chabahar, Iran;2. Department of Chemistry, Faculty of Sciences, Shahid Chamran University, Ahvaz, Iran;3. National Iranian Drilling Company (NIDC), Drilling Fluids Services and Waste Management, Research and Development Section, Ahvaz, Iran;4. ACECR-Production Technology Research Institute, Ahvaz, Iran;5. Department of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland;1. Instituto de Investigación para La Gestión Integrada de Zonas Costeras, Campus de Gandía, Universitat Politècnica de València, C/ Paranimf 1, 46730, Grao de Gandía, Valencia, Spain;2. Department of Analytical Chemistry, Universitat de València, Dr. Moliner 50, 46100, Burjassot, Valencia, Spain;1. Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1, build.3, 119991 Moscow, Russian Federation;2. A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova St. 28, 119991 Moscow, Russian Federation;3. P. N. Lebedev Physical Institute, Leninsky prosp. 53, 119991 Moscow, Russian Federation;4. Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 6, D-76131 Karlsruhe, Germany;5. Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-Leopoldshafen, Germany;6. Evoled Ltd., Puskina iela, 1a-24, Riga, Latvia
Abstract:The purpose of the current study was to analyse apoptosis and bcl-2 expression in laryngeal squamous cell carcinoma (SCC) with special reference to their prognostic significance, correlation with the clinical and pathological characteristics as well as cell proliferation and p53 accumulation. 172 patients with primary laryngeal SCC were followed-up for a median of 67 months. The volume corrected apoptotic (A/V) index was analysed using an in situ end labelling method (TUNEL) in 85 randomly selected patients. The expression of bcl-2 and p53 was analysed with monoclonal antibodies. The proliferative activity was measured both with Ki-67 (MIB-1) antibody and the volume corrected mitotic (M/V) index. The A/V index was not associated with p53 (P=0.6) or bcl-2 (P=0.6) expression or with proliferative parameters (P=0.9 for M/V and P=0.3 for MIB-1). The 10-year overall survival in patients with a high A/V index was poorer when compared with patients with a low index (47% versus 81%, P=0.005), while accumulation of bcl-2 had no prognostic significance (P=0.5). In Cox multivariate analysis of the whole cohort, stage (P<0.0005) and histological grade (P=0.04) were predictors of overall survival. In the subset of patients with an A/V index available, predictors of survival were stage (P=0.05), A/V index (P=0.02) and histological grade (P=0.04). A high A/V index was an independent predictor of poor survival in laryngeal SCC. This effect was not associated with tumour cell proliferation. Accumulations of p53 and bcl-2 were not associated with apoptosis. Expression of bcl-2 lacks any prognostic significance in laryngeal SCC. We propose that assessment of the A/V index may help in selecting patients with poor prognosis.
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