1. ¹Academic Department of Radiation Oncology, The University of Manchester, Christie Hospital NHS Trust, Manchester M20 4BX, UK
2. ²Department of Clinical Oncology, Christie Hospital NHS Trust, Manchester M20 4BX, UK
3. ³Experimental Oncology Group, School of Pharmacy and Pharmaceutical Sciences, The University of Manchester, Oxford Road, Manchester M13 9PL, UK

Correspondence: Dr CML West, E-mail: catharine.west@manchester.ac.uk

Received 16 August 2005; Accepted 27 October 2005; Published online 29 November 2005.

Abstract

The expression of hypoxia-regulated genes promotes an aggressive tumour phenotype and is associated with an adverse cancer treatment outcome. Thymidine phosphorylase (TP) levels increase under hypoxia, but the protein has not been studied in association with hypoxia in human tumours. An investigation was made, therefore, of the relationship of tumour TP with hypoxia, the expression of other hypoxia-associated markers and clinical outcome. This retrospective study was carried out in patients with locally advanced cervical carcinoma who underwent radiotherapy. Protein expression was evaluated with immunohistochemistry. Hypoxia was measured using microelectrodes and the level of pimonidazole binding. There was no relationship of TP expression with tumour pO₂ (r=-0.091, P=0.59, n=87) or pimonidazole binding (r=0.13, P=0.45, n=38). There was no relationship between TP and HIF-1, but there was a weak borderline significant relationship with HIF-2 expression. There were weak but significant correlations of TP with the expression of VEGF, CA IX and Glut-1. In 119 patients, the presence of TP expression predicted for disease-specific (P=0.032) and metastasis-free (P=0.050) survival. The results suggest that TP is not a surrogate marker of hypoxia, but is linked to the expression of hypoxia-associated genes and has weak prognostic power.