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A possible role of thymidine phosphorylase expression and5‐fluorouracil increased sensitivity in oropharyngeal cancer patients

2007; Wiley; Volume: 11; Issue: 2 Linguagem: Inglês

10.1111/j.1582-4934.2007.00007.x

1582-4934

Girolamo Ranieri, Luciano Grammatica, Rosa Patruno, Alfredo Zito, Paolo Valerio, S. Iacobellis, Cosmo Damiano Gadaleta, Giampietro Gasparini, Doménico Ribatti,

Acute Myeloid Leukemia Research

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.