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Higher expression of deoxyuridinetriphosphatase (dUTPase) may predict the metastasis potential of colorectal cancer
  1. Akihiko Kawahara (akihiko4{at}med.kurume-u.ac.jp)
  1. Department of Diagnostic Pathology, Kurume University Hospital, Japan
    1. Yoshito Akagi
    1. Department of Surgery, Kurume University School of Medicine, Japan
      1. Satoshi Hattori
      1. Biostatistics Center, Kurume University, Kurume, Japan
        1. Tomoaki Mizobe
        1. Department of Surgery, Kurume University School of Medicine, Japan
          1. Kazuo Shirouzu
          1. Department of Surgery, Kurume University School of Medicine, Japan
            1. Mayumi Ono
            1. Department of Pharmaceutical Oncology, Graduate School of Pharmaceutical Sciences, Kyushu University, Japan
              1. Takashi Yanagawa
              1. Biostatistics Center, Kurume University, Kurume, Japan
                1. Michihiko Kuwano
                1. Innovation Center for Medical Redox Navigation, Kyushu University, Japan
                  1. Masayoshi Kage
                  1. Department of Diagnostic Pathology, Kurume University Hospital, Japan

                    Abstract

                    Aims: 5-Fluorouracil (5-FU) is one of the most widely used anti-cancer drugs; however, the activity of 5-FU is determined by the presence of several enzymes that limit its activation or degradation and those include dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), thymidine kinase (TK), thymidine phosphorylase (TP) and deoxyuridine triphosphatase (dUTPase). We compared the expression levels of these enzymes between the primary colorectal cancer of patients with and without distant metastases. Furthermore, we compared these expression levels between the primary tumor and the corresponding metastasis.

                    Methods: Of 55 patients with colorectal cancers, 20 with no metastasis and the other 35 had distant metastasis. A strong expression was classified as positive, while weak to moderate or no expression was negative by immunohistochemistry.

                    Results: Of the six 5-FU-related enzymes, the expressions of dUTPase (p=0.005), TK (p=0.019), and DPD (p=0.033) were significantly different in primary tumors with metastasis from those with non-metastasis. The altered expression of OPRT (34.3%), TS (40.0%) and dUTPase (42.9%) was significantly great from primary to metastasis, among the 35 patients with metastasis. By contrast, a comparative rate of tumors also lost the expression of OPRT, TS and dUTPase in metastatic deposits in 6, 5, and 7 patients, respectively.

                    Conclusions: From our comparative study of the six 5-FU-related enzymes in colorectal cancer, the expression of dUTPase was most significantly different between primary tumors and their corresponding metastatic tumor. We suggest that dUTPase may be a predictive biomarker for the metastatic potential of colorectal cancer.

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