Expression of thymidylate synthase and thymidine phosphorylase in human breast carcinoma: implication for method to detect expression of these molecules in clinic.

Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor, and has an angiogenic activity in experimental models and human solid tumors. A critical step in the de novo pathway of DNA synthesis is the production of the pyrimidine nucleotide dTMP from dump and this reaction is catalyzed by thymidylate synthase (TS). Both dThdPase and TS levels seemed to be related to response to 5-fluorouracil (5-FU) therapy in different types of human solid tumors. The present study evaluated dThdPase and TS expression levels by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR), using a same set of 39 breast carcinoma tissues for both methods. An inverted-relationship in the expression levels of TS and dThdPase was observed. Further, immunohistochemical analysis may be a better tool than analysis by RT-PCR in detection of dThdPase and TS, because of both dThdPase and TS expression in cells besides carcinoma cells. These imply that immunohistochemical analysis of dThdPase and TS is available for selection of patients who will be received 5-FU based chemotherapy.