A possible role of thymidine phosphorylase expression and 5-fluorouracil increased sensitivity in oropharyngeal cancer patients.
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.
Ranieri
G
G
Department of Experimental Oncology, Unit of Interventional Radiology, Department of Critical Area and Surgery; National Cancer Institute of Bari, Bari, Italy.
Grammatica
L
L
Patruno
R
R
Zito
A F
AF
Valerio
P
P
Iacobellis
S
S
Gadaleta
C
C
Gasparini
G
G
Ribatti
D
D
D017677:Age Distribution; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D007971:Leukoplakia / Q000473:pathology; D008297:Male; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D013939:Thymidine Phosphorylase / Q000378:metabolism*
D013939:Thymidine Phosphorylase; D005472:Fluorouracil