A possible role of thymidine phosphorylase expression and 5-fluorouracil increased sensitivity in oropharyngeal cancer patients.

Abstract

Thymidine Pi deoxyribosyltransferase (TP) is an enzyme involved in DNA synthesis up-regulated in tumours and it is also a pro-angiogenic factor. TP cannot activate capecitabine, because capecitabine first needs conversion by carboxylesterase and cytidine deaminase into 5-deoxy-fluorouridine. This compound can be activated by TP to 5-fluorouracil (5-FU). Although TP is not necessary for 5-FU toxicity, experimental data suggest that high levels of TP correlate with an enhanced response to 5-FU therapy. In this study, we have analysed by immunohistochemistry CD34, CD68 and TP positive cells in bioptic samples from 53 patients with T(1-3) N(0-1) M(0) oropharyngeal squamous cell carcinoma (OSC) and from 24 patients with non-dysplastic oropharyngeal leukoplakia (NDOLP). Results showed that the mean of TP-positive cells, CD68 positive macrophages and CD34 positive endothelial cells eval-uated as microvessel density (MVD) was significantly higher in OSC than in NDOLP. Moreover, at a median follow-up of 19 months, patients with TP expression and higher MVD showed a better survival rate as compared to those with low MVD, probably as a consequence of 5-FU-based therapy.We hypothesized a role for TP in oropharyngeal tumourigenesis and 5-FU activation in the adjuvant setting of OSC patients.

• Authors: G Ranieri, L Grammatica, R Patruno, A F Zito, P Valerio, S Iacobellis, C Gadaleta, G Gasparini, D Ribatti
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) 2007 Mar-Apr Vol. 11 Issue 2 Pg. 362-8 ISSN: 1582-1838 [Print] England
• PMID: 17378915 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Thymidine Phosphorylase
• Fluorouracil

Topics

• Age Distribution
• Aged
• Carcinoma, Squamous Cell (drug therapy, metabolism, pathology)
• Case-Control Studies
• Female
• Fluorouracil (therapeutic use)
• Humans
• Immunohistochemistry
• Leukoplakia (pathology)
• Male
• Oropharyngeal Neoplasms (drug therapy, metabolism, pathology)
• Thymidine Phosphorylase (metabolism)