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Neo-angiogenesis in locally advanced squamous cell head and neck cancer correlates with thymidine phosphorylase expression and p53 nuclear oncoprotein accumulation
Authors:Alexandra Giatromanolaki  George Fountzilas  Michael I Koukourakis  Petroula Arapandoni  Varvara Theologi  Stylianos Kakolyris  Vassilios Georgoulias  Adrian L Harris  Kevin C Gatter
Affiliation:(1) Department of Radiotherapy - Oncology and Laboratory of Cancer Biology, University Hospital of Iraklion, Iraklion 71110, PO BOX 1352, Crete, Greece;(2) Tumour and Angiogenesis Research Group, 18 Dimokratias Avenue, Iraklion, 71306 Crete, Greece;(3) Department of Medical Oncology, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, 54006, Greece;(4) Department of Pathology, METAXA Cancer Hospital, Pireus, Greece;(5) Departments of Cellular Science and ICRF Medical Oncology Unit, Oxford Radcliffe Hospital, Headington Oxford, OX3 7LJ, UK
Abstract:
Thymidine phosphorylase (Th.P) is an angiogenic factor shown to induce endothelial cell migration and proliferation. On the other hand, loss of wild type p53 function leads to down-regulation of thrombospondin-1, an inhibitor of angiogenesis. In this immunohistochemical study we investigated the intratumoural angiogenesis and thymidine phosphorylase (Th.P) expression in paraffin-embedded bioptical material from 104 locally advanced squamous cell head and neck cancers. The nuclear accumulation of mutant p53 protein and the cytoplasmic expression of bcl-2 protein was also assessed. High vascular grade was observed in 56% and high Th.P tumour cell reactivity in 48% of cases. High microvessel score was associated with an increased percentage of cancer cells expressing thymidine phosphorylase (P = 0.001). Increased p53 nuclear accumulation also corre-lated with high vascular grade (P = 0.001). High histological grade and absence of bcl-2 overexpression were associated with lymph node involvement (P = 0.002 and P = 0.02 respectively). No correlation of clinically detected lymphadenopathy with angiogenesis and p53 was observed. We conclude that intense neo-angiogene-sis in locally advanced squamous cell head neck cancer is a frequent event, which is associated with nuclear p53 accumulation and thymidine phosphorylase overexpression. ©Lippincott Williams & Wilkins
Keywords:angiogenesis  thymidine phosphorylase  p53  bcl-2  head and neck cancer
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