[Expression of dihydropyrimidine dehydrogenase in primary colorectal cancer and liver metastasis--a relationship between mRNA levels in cancer cells and protein levels in cancerous tissue and effect of 5-fluorouracil].
OBJECTIVE
To compare mRNA levels in cancer cells and protein levels in cancerous tissue in order to evaluate the expression of dihydropyrimidine dehydrogenase (DPD).


METHODS
The materials were resected specimens of primary colorectal cancer (n=88) and synchronous liver metastasis (n=15). The expression of DPD mRNA in cancer cells was quantified by reverse-transcriptase polymerase chain reaction (RT-PCR) using cancer cells obtained by micro-dissection of paraffin-embedded specimens (Danenberg tumor profiling method). The protein level of DPD was determined by enzyme -linked immunosorbent assay (ELISA).


RESULTS
There was no relationship between the level of DPD mRNA and the level of DPD protein in primary colorectal cancers and liver metastases. The level of DPD protein tended to be higher in liver metastases than in primary lesions (p=0.08) without a significant relationship between the two values. There was no relationship between primary colorectal lesions and liver metastases in terms of the expression of DPD mRNA. The efficacy of 5-fluorouracil (5-FU or UFT)/Leucovorin did not correlate with the expression level of DPD mRNA or DPD protein of primary lesions (n=18).


CONCLUSIONS
We should note the discrepancy of results between the two different methods and the lack of a relationship between the levels of DPD expression in primary lesions and liver metastases, when considering the efficacy of 5-FU-based regimens according to the DPD expression level in primary colorectal cancers.
Ishibashi
Keiichiro
K
Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University.
Sobajima
Jun
J
Ishiguro
Toru
T
Ohsawa
Tomonori
T
Okada
Norimichi
N
Miyazaki
Tatsuya
T
Yokoyama
Masaru
M
Inokuma
Shigehisa
S
Ishida
Hideyuki
H
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000201:enzymology*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000494:pharmacology; D008113:Liver Neoplasms / Q000201:enzymology* / Q000556:secondary*; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000964:Antimetabolites, Antineoplastic; D011506:Proteins; D012333:RNA, Messenger; D042943:Dihydrouracil Dehydrogenase (NADP); D002955:Leucovorin; D005472:Fluorouracil