RESEARCH – May 2006

Application of analysis of thymidine phosphorylase expression in metastatic renal carcinoma tissue


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Thymidine phosphorylase is the enzyme that metabolizes 5’-deoxy-5-fluorouridine, an intermediate metabolite of capecitabine, to the active drug 5-fluorouracil. Capecitabine is a fluoropyrimidine carbamate capable of exploiting high concentrations of thymidine phosphorylase in the tumour tissue to achieve activation preferentially at the tumour site. Purpose of the study was to implement analysis of thymidine phosphorylase expression in the renal cell carcinoma tissue using immunohistochemistry assays with the monoclonal anti-thymidine phosphorylase antibody, for evaluating the level of thymidine phosphorylase expression and possible correlation between thymidine expression values and treatment efficacy of a combination of capecitabine and interferon alfa-2a.
Methods. Thymidine phosphorylase expression was evaluated in the tumour tissue of 16 patients. Semiquantitative analysis using a scoring system for tumour cells was performed, where scores were calculated as the sum of the staining percentage and the staining intensity scores, ranging from 0 to 7. Capecitabine was  administered orally at a dose 1,250 mg/m2 twice daily for 14 days followed by 7 days of rest, interferon alfa-2a was administered subcutaneously 6 million units three times weekly. Results. Overall partial response rate in this group of patients was 31%, stable disease status was additionally achieved in 33% of the patients. Substantial thymidine phosphorylase expression in the tumour tissue was detected in majority of patients, 4 patients had the semi-quantitative score 2 or 3 and in 12 patients it was 4 to 6. No correlation was observed between thymidine phosphorylase expression and response to treatment with capecitabine and interferon alfa-2a in the analysed group of patients.
Conclusion. Evaluation of thymidine phosphorylase in the renal cell carcinoma tissue with immunohistochemistry assays is an applicable method in everyday clinical practice. Further larger study is necessary to define the exact prognostic and predictive value of thymidine phosphorylase in the renal cell carcinoma tissue.