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 hi-her 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.