Intratumoral dihydropyrimidine dehydrogenase messenger RNA level reflects tumor progression in human colorectal cancer

Ann Surg Oncol. 2002 Jul;9(6):599-603. doi: 10.1007/BF02573898.

Abstract

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.

MeSH terms

  • Aged
  • Antimetabolites, Antineoplastic / pharmacology
  • Biomarkers
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Dihydrouracil Dehydrogenase (NADP)
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Female
  • Fluorouracil / pharmacology
  • Humans
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary*
  • Male
  • Middle Aged
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • RNA, Messenger / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Statistics, Nonparametric

Substances

  • Antimetabolites, Antineoplastic
  • Biomarkers
  • RNA, Messenger
  • Oxidoreductases
  • Dihydrouracil Dehydrogenase (NADP)
  • Fluorouracil