Intratumoral dihydropyrimidine dehydrogenase messenger RNA level reflects tumor progression in human colorectal cancer.
BACKGROUND
Determination of intratumoral dihydropyrimidine dehydrogenase (DPD) is of clinical interest because increased DPD levels can influence the tumor response to 5-fluorouracil-based chemotherapy through increased inactivation of the agent in tumor cells.


METHODS
DPD messenger RNA (mRNA) levels were evaluated in 80 consecutive patients undergoing surgery for primary colorectal cancer and 12 cases of liver metastasis.


RESULTS
Higher DPD mRNA levels were associated with higher pathologic classification, corresponding to the T categories (r =.267; P =.003). The DPD mRNA level was statistically higher in tumors with microscopic lymph node metastasis than in those without (P =.002). Hence, the DPD mRNA level increased in accordance with Dukes' classification (r =.387; P =.0001). The DPD mRNA level of the liver metastasis from colorectal cancer was significantly higher than that of primary lesions (P =.002). In eight patients, the DPD mRNA level of the liver metastasis was significantly higher than that of the matched primary tumor (P =.017).


CONCLUSIONS
Increases of the DPD mRNA level in cancerous tissue seem to reflect tumor progression. High DPD mRNA levels in liver metastasis and advanced colorectal cancer may have clinical importance for 5-fluorouracil-based chemosensitivity.
Shirota
Yoshinori
Y
Department of Digestive Surgery, Tokyo Medical and Dental University, Japan. y-shirota.srg2@tmd.ac.jp
Ichikawa
Wataru
W
Uetake
Hiroyuki
H
Yamada
Hiroyuki
H
Nihei
Zenro
Z
Sugihara
Kenichi
K
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D015415:Biomarkers; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP); D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
D000964:Antimetabolites, Antineoplastic; D015415:Biomarkers; D012333:RNA, Messenger; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil