Correlation between thymidylate synthase and dihydropyrimidine dehydrogenase mRNA level and in vitro chemosensitivity to 5-fluorouracil, in relation to differentiation in gastric cancer.
OBJECTIVE
It has been suggested that the gene expression levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) help in the prediction of the response to 5-fluorouracil (5-FU) in vivo and in vitro in gastric cancers.


METHODS
In this study, intratumoral TS and DPD gene expressions were evaluated with real time reverse transcriptional polymerase chain reaction technique to determine the correlation between the expression of these two genes and in vitro sensitivity to 5-FU, assessed by the histoculture drug response assay on 87 patients with gastric adenocarcinoma.


RESULTS
The sensitivity to 5-FU did not show any difference in clinicopathological groups. DPD gene level was higher in undifferentiated (n = 39) than differentiated (n = 48) tumors (P = 0.043). In differentiated tumors, TS gene expression levels were higher in the tumors with relative resistance to 5-FU, while in undifferentiated cases, DPD mRNA levels were higher in tumors that showed resistance to 5-FU in vitro (P = 0.043 and 0.007, respectively). DPD also had significant predictive value for 5-FU sensitivity in undifferentiated cases [R(S) = -0.401, P = 0.011]. TS and DPD gene expression levels were more highly correlated in undifferentiated compared to differentiated cases [R(S) = 0.515 and 0.359, respectively].


CONCLUSIONS
Different gene expression might be responsible for 5-FU sensitivity in gastric cancers of different histologic origin.
Fakhrejahani
Elham
E
Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki-shi, Osaka 569-8686, Japan.
Miyamoto
Akiko
A
Tanigawa
Nobuhiko
N
D000328:Adult; D002454:Cell Differentiation / Q000502:physiology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D013940:Thymidylate Synthase / Q000235:genetics*
D012333:RNA, Messenger; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D005472:Fluorouracil