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Annals of Surgical Oncology 9:599-603 (2002)
© 2002 Society of Surgical Oncology


ORIGINAL ARTICLES

Intratumoral Dihydropyrimidine Dehydrogenase Messenger RNA Level Reflects Tumor Progression in Human Colorectal Cancer

Yoshinori Shirota, MD, Wataru Ichikawa, MD, Hiroyuki Uetake, MD, Hiroyuki Yamada, MD, Zenro Nihei, MD and Kenichi Sugihara, MD

From the Department of Digestive Surgery (YS, HU, HY, ZN, KS), Tokyo Medical and Dental University, Tokyo, Japan; and the Second Department of Surgery (WI), Saitama Medical School, Saitama, Japan.

Correspondence: Address correspondence and reprint requests to: Yoshinori Shirota, MD, Department of Digestive Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Fax: 81-3-5803-0139; E-mail: y-shirota.srg2{at}tmd.ac.jp

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.

Key Words: Dihydropyrimidine dehydrogenase • 5-Fluorouracil • Reverse transcription-polymerase chain reaction • Messenger RNA level • Colorectal cancer • Metastatic liver tumors







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