Neo-angiogenesis in locally advanced squamous cell head and neck cancer correlates with thymidine phosphorylase expression and p53 nuclear oncoprotein accumulation

Clin Exp Metastasis. 1998 Oct;16(7):665-72. doi: 10.1023/a:1006554512338.


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 correlated 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-angiogenesis in locally advanced squamous cell head neck cancer is a frequent event, which is associated with nuclear p53 accumulation and thymidine phosphorylase overexpression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / blood supply*
  • Carcinoma, Squamous Cell / metabolism*
  • Female
  • Head and Neck Neoplasms / blood supply*
  • Head and Neck Neoplasms / metabolism*
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mutation
  • Neovascularization, Pathologic / metabolism*
  • Observer Variation
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Thymidine Phosphorylase / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*


  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • Thymidine Phosphorylase