Abstract 5572: Prognostic significance of TS, TK, OPRT and DPD activities in renal cell carcinoma

Abstract

Abstract Introduction: Thymidylate synthase (TS) and thymidine kinase (TK) are the key enzymes in the de novo and salvage DNA synthetic process, respectively. Orotate phosphoribosyltransferase (OPRT) plays an important role in the de novo pathway of DNA and RNA synthesis. In contrast, dihydropyrimidine dehydrogenase (DPD) is a key enzyme involved in degradation of DNA and RNA. We examined the activities of TS, TK, OPRT and DPD in 83 renal cell carcinomas and normal kidneys and evaluated the clinical significance. Methods: TS, TK, OPRT and DPD activities in non-fixed fresh frozen renal cell carcinomas and normal kidneys were determined enzymatically by the FdUMP binding assay, the DEAE cellulose disc method, the 5-FU phosphorylation assay and the 5-FU degradation assay, respectively. Results: TS activity was 5-fold higher in renal cell carcinoma compared to normal kidney. TS activity in Stage III/IV renal cell carcinoma was 3-fold higher than that in Stage I/II renal cell carcinoma. In addition, the level of TS activity in Grade 3 renal cell carcinoma was 2-fold higher than that in Grade 1 and Grade 2 carcinomas. TK activity was approximately 4-fold higher in normal kidney compared with renal cell carcinoma. TK activity in Stage IV renal cell carcinoma was 2-fold higher than that in Stage I-III renal cell carcinoma. Furthermore, the level of TK activity in Grade 3 renal cell carcinoma was 2-fold higher than that in Grade 1 and Grade 2 carcinomas. OPRT activity was approximately 7-fold higher in renal cell carcinoma compared to normal kidney. OPRT activity in Stage III/IV renal cell carcinoma was 2-fold higher than that in Stage I/II renal cell carcinoma. The level of OPRT activity in Grade 3 renal cell carcinoma was 3-fold higher than those in Grade 1 and Grade 2 carcinomas. DPD activity was approximately 2-fold higher in normal kidney compared to renal cell carcinoma. The higher stage and grade of renal cell carcinoma was, the lower DPD activity was observed. The level of OPRT activity correlated with those of TS and TK activities. However, DPD activity was not associated with TS activity. High TS, TK, OPRT activities and low DPD activity predicted worse prognosis in patients with renal cell carcinoma.Conclusions: The present study has demonstrated that TS, TK, OPRT and DPD activities in renal cell carcinoma correlated with the stage/grade status of renal cell carcinoma. In addition, the levels of TS, TK, OPRT and DPD activities were prognostic parameters in patients with renal cell carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5572. doi:1538-7445.AM2012-5572