The discrepancy in thymidylate synthase and dihydropyrimidine dehydrogenase expression depending on measurement methodologies in stage 4 gastric cancer.

BACKGROUND/AIMS: Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are reported to be a major determinant of variations in the sensitivity for fluoropyrimidines in gastric cancer. The aim of this study was to investigate whether there is a discrepancy in the TS and DPD expression depending on measuring method.

METHODOLOGY

The protein levels and mRNA level of TS and DPD were estimated in primary gastric cancer tissue specimens after a non-curative resection. The protein levels were determined by ELISA from frozen tissue specimens. The gene expressions were measured using real-time reverse transcriptional polymerase chain reaction (RT-PCR). For the extraction of RNA, laser-captured microdissection (LCM) was performed in formalin-fixed paraffin-embedded (FFPE) specimens.

RESULTS

There was no correlation between the protein levels and mRNA levels of TS and DPD. The protein levels and mRNA expression levels were not correlated with survival. High levels of TS mRNA showed a trend toward reduced survival (p=0.074).

CONCLUSIONS

The discrepancy in TS and DPD expressions depending on the measurement methodologies utilized should thus be emphasized in these far advanced gastric cancer patients.