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Annals of Oncology 11:273-279, 2000
© 2000 European Society for Medical Oncology


research-article

Characterization of dihydropyrimidine dehydrogenase on immunohisto-chemistry in colon carcinoma, and correlation between immunohisto-chemical score and protein level or messenger RNA expression

T. Takenoue1,, J. Kitayama1, Y. Takei1, N. Umetani1, K. Matsuda1, M. E. Nita1, K. Hatano1, T. Tsuruo2 and H. Nagawa1

1Department ofSurgical Oncology, The University of Tokyo Hongo
2Institute of Molecular and Cellular Biosciences, The University of Tokyo Yayoi, Bunkyo-ku, Tokyo, Japan

Correspondence to: T. Takenoue, MD, Department Of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail: takenoue-lsu{at}h.u-tokyo.ac.jp

Background: Dihydropyrimidine dehydrogenase (DPD) is the first enzyme that metabolizes 5-fluorouracil (5-FU). Until now, enzymatic activity or mRNA expression of DPD has been investigated. However, there are no papers on immunohisto-chemical evaluation of DPD. We investigated DPD staining on immunohistochemistry, and examined the relationship among immunohistochemical score, protein level and mRNA expression of DPD.

Materials and methods: Forty-seven resected colon cancer specimens, four colon cancer cell lines, two xenografts by colon cancer cell lines, and human mononuclear cells were used. Immunohistochemistry was performed using DPD monoclonal antibody. Protein levels were determined by Western blot analysis. And mRNA levels were calculated by semi-quantitative reverse transcription polymerase chain reaction (RT–PCR).

Results: DPD was strongly expressed in the cytoplasm of cancer cells, and in the cytoplasm of macrophage and plasma cells. The immunohistochemical score was more correlated with protein levels (P = 0.0054) than mRNA expression (P = 0.9028).

Conclusions: We investigated the characterization of DPD immunohistochemically, and showed that immunohistochemical expression of DPD can be used to predict the sensitivity of colorectal carcinomas to 5-FU.

DPD, 5-fluorouracil, immunohistochemistry, RT–PCR, Western blotting


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