Immunohistochemical demonstration of fluoropyrimidine-metabolizing enzymes in various types of cancer.

Shingo Kamoshida, Kazuya Shiogama, Ryoichi Shimomura, Ken Ichi Inada, Yoichi Sakurai, Masahiro Ochiai, Hiroshi Matuoka, Kotaro Maeda, Yutaka Tsutsumi

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Fluoropyrimidines [5-Fluorouracil (5-FU) and its prodrugs] have been widely used in the treatment of solid cancers. The anticancer effects primarily depend on intratumoral levels of enzymes metabolizing the drugs, such as dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS). In order to know the tumor types susceptible to respective fluoropyrimidines, we investigated the expression of DPD, OPRT, TP and TS in various types of cancer with the immunoperoxidase method. These four enzymes existed in all of the cancer types studied, such as pulmonary, gastric, colorectal, hepatic, cholecystic, pancreatic, renal, urocystic, and mammary cancers. Respective types of cancers presented characteristic immunohistochemical features as follows: pulmonary adenocarcinoma, DPD- and TP-high; pulmonary squamous cell carcinoma, TS- and TP-high; intestinal-type gastric adenocarcinoma, TP-high; diffuse-type gastric adenocarcinoma, DPD-low and TS-high; colorectal adenocarcinoma, DPD- and TP-low, hepatocellular carcinoma, DPD-high, and TS- and OPRT-low; cholecystic adenocarcinoma, DPD- and TS-high; renal cell carcinoma, DPD-low, and OPRT- and TP-high; urocystic transitional cell carcinoma, DPD-high and OPRT-low; and mammary ductal carcinoma, OPRT-low, and TS- and TP-high. The enzyme expression pattern in cancer tissue was generally similar to that of their normal counterparts. However, TP immunoreactivity in adenocarcinomas of the lung, stomach and gallbladder, and urothelial carcinoma of the urinary bladder was stronger, and DPD immunoreactivity in adenocarcinoma of the breast was weaker, when compared with normal epithelial cells. Non-epithelial cells were also positive for these enzymes. These results indicated that the key enzymes influencing the effects of fluoropyrimidines differ from cancer to cancer. Fluoropyrimidine treatment may be selected, based on the simultaneous immunohistochemical evaluation of the fluoropyrimidine metabolic enzymes.

Original languageEnglish
Pages (from-to)1223-1230
Number of pages8
JournalOncology Reports
Volume14
Issue number5
Publication statusPublished - 01-01-2005

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Dihydrouracil Dehydrogenase (NADP)
Thymidine Phosphorylase
Orotate Phosphoribosyltransferase
Thymidylate Synthase
Enzymes
Neoplasms
Adenocarcinoma
Stomach
Gallbladder
Urinary Bladder
Carcinoma, Ductal, Breast
Gallbladder Neoplasms
Transitional Cell Carcinoma
Kidney Neoplasms
Prodrugs
Liver Neoplasms
Pancreatic Neoplasms
Renal Cell Carcinoma
Urinary Bladder Neoplasms
Fluorouracil

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kamoshida, S., Shiogama, K., Shimomura, R., Inada, K. I., Sakurai, Y., Ochiai, M., ... Tsutsumi, Y. (2005). Immunohistochemical demonstration of fluoropyrimidine-metabolizing enzymes in various types of cancer. Oncology Reports, 14(5), 1223-1230.
Kamoshida, Shingo ; Shiogama, Kazuya ; Shimomura, Ryoichi ; Inada, Ken Ichi ; Sakurai, Yoichi ; Ochiai, Masahiro ; Matuoka, Hiroshi ; Maeda, Kotaro ; Tsutsumi, Yutaka. / Immunohistochemical demonstration of fluoropyrimidine-metabolizing enzymes in various types of cancer. In: Oncology Reports. 2005 ; Vol. 14, No. 5. pp. 1223-1230.
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abstract = "Fluoropyrimidines [5-Fluorouracil (5-FU) and its prodrugs] have been widely used in the treatment of solid cancers. The anticancer effects primarily depend on intratumoral levels of enzymes metabolizing the drugs, such as dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS). In order to know the tumor types susceptible to respective fluoropyrimidines, we investigated the expression of DPD, OPRT, TP and TS in various types of cancer with the immunoperoxidase method. These four enzymes existed in all of the cancer types studied, such as pulmonary, gastric, colorectal, hepatic, cholecystic, pancreatic, renal, urocystic, and mammary cancers. Respective types of cancers presented characteristic immunohistochemical features as follows: pulmonary adenocarcinoma, DPD- and TP-high; pulmonary squamous cell carcinoma, TS- and TP-high; intestinal-type gastric adenocarcinoma, TP-high; diffuse-type gastric adenocarcinoma, DPD-low and TS-high; colorectal adenocarcinoma, DPD- and TP-low, hepatocellular carcinoma, DPD-high, and TS- and OPRT-low; cholecystic adenocarcinoma, DPD- and TS-high; renal cell carcinoma, DPD-low, and OPRT- and TP-high; urocystic transitional cell carcinoma, DPD-high and OPRT-low; and mammary ductal carcinoma, OPRT-low, and TS- and TP-high. The enzyme expression pattern in cancer tissue was generally similar to that of their normal counterparts. However, TP immunoreactivity in adenocarcinomas of the lung, stomach and gallbladder, and urothelial carcinoma of the urinary bladder was stronger, and DPD immunoreactivity in adenocarcinoma of the breast was weaker, when compared with normal epithelial cells. Non-epithelial cells were also positive for these enzymes. These results indicated that the key enzymes influencing the effects of fluoropyrimidines differ from cancer to cancer. Fluoropyrimidine treatment may be selected, based on the simultaneous immunohistochemical evaluation of the fluoropyrimidine metabolic enzymes.",
author = "Shingo Kamoshida and Kazuya Shiogama and Ryoichi Shimomura and Inada, {Ken Ichi} and Yoichi Sakurai and Masahiro Ochiai and Hiroshi Matuoka and Kotaro Maeda and Yutaka Tsutsumi",
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Kamoshida, S, Shiogama, K, Shimomura, R, Inada, KI, Sakurai, Y, Ochiai, M, Matuoka, H, Maeda, K & Tsutsumi, Y 2005, 'Immunohistochemical demonstration of fluoropyrimidine-metabolizing enzymes in various types of cancer.', Oncology Reports, vol. 14, no. 5, pp. 1223-1230.

Immunohistochemical demonstration of fluoropyrimidine-metabolizing enzymes in various types of cancer. / Kamoshida, Shingo; Shiogama, Kazuya; Shimomura, Ryoichi; Inada, Ken Ichi; Sakurai, Yoichi; Ochiai, Masahiro; Matuoka, Hiroshi; Maeda, Kotaro; Tsutsumi, Yutaka.

In: Oncology Reports, Vol. 14, No. 5, 01.01.2005, p. 1223-1230.

Research output: Contribution to journalArticle

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T1 - Immunohistochemical demonstration of fluoropyrimidine-metabolizing enzymes in various types of cancer.

AU - Kamoshida, Shingo

AU - Shiogama, Kazuya

AU - Shimomura, Ryoichi

AU - Inada, Ken Ichi

AU - Sakurai, Yoichi

AU - Ochiai, Masahiro

AU - Matuoka, Hiroshi

AU - Maeda, Kotaro

AU - Tsutsumi, Yutaka

PY - 2005/1/1

Y1 - 2005/1/1

N2 - Fluoropyrimidines [5-Fluorouracil (5-FU) and its prodrugs] have been widely used in the treatment of solid cancers. The anticancer effects primarily depend on intratumoral levels of enzymes metabolizing the drugs, such as dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS). In order to know the tumor types susceptible to respective fluoropyrimidines, we investigated the expression of DPD, OPRT, TP and TS in various types of cancer with the immunoperoxidase method. These four enzymes existed in all of the cancer types studied, such as pulmonary, gastric, colorectal, hepatic, cholecystic, pancreatic, renal, urocystic, and mammary cancers. Respective types of cancers presented characteristic immunohistochemical features as follows: pulmonary adenocarcinoma, DPD- and TP-high; pulmonary squamous cell carcinoma, TS- and TP-high; intestinal-type gastric adenocarcinoma, TP-high; diffuse-type gastric adenocarcinoma, DPD-low and TS-high; colorectal adenocarcinoma, DPD- and TP-low, hepatocellular carcinoma, DPD-high, and TS- and OPRT-low; cholecystic adenocarcinoma, DPD- and TS-high; renal cell carcinoma, DPD-low, and OPRT- and TP-high; urocystic transitional cell carcinoma, DPD-high and OPRT-low; and mammary ductal carcinoma, OPRT-low, and TS- and TP-high. The enzyme expression pattern in cancer tissue was generally similar to that of their normal counterparts. However, TP immunoreactivity in adenocarcinomas of the lung, stomach and gallbladder, and urothelial carcinoma of the urinary bladder was stronger, and DPD immunoreactivity in adenocarcinoma of the breast was weaker, when compared with normal epithelial cells. Non-epithelial cells were also positive for these enzymes. These results indicated that the key enzymes influencing the effects of fluoropyrimidines differ from cancer to cancer. Fluoropyrimidine treatment may be selected, based on the simultaneous immunohistochemical evaluation of the fluoropyrimidine metabolic enzymes.

AB - Fluoropyrimidines [5-Fluorouracil (5-FU) and its prodrugs] have been widely used in the treatment of solid cancers. The anticancer effects primarily depend on intratumoral levels of enzymes metabolizing the drugs, such as dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS). In order to know the tumor types susceptible to respective fluoropyrimidines, we investigated the expression of DPD, OPRT, TP and TS in various types of cancer with the immunoperoxidase method. These four enzymes existed in all of the cancer types studied, such as pulmonary, gastric, colorectal, hepatic, cholecystic, pancreatic, renal, urocystic, and mammary cancers. Respective types of cancers presented characteristic immunohistochemical features as follows: pulmonary adenocarcinoma, DPD- and TP-high; pulmonary squamous cell carcinoma, TS- and TP-high; intestinal-type gastric adenocarcinoma, TP-high; diffuse-type gastric adenocarcinoma, DPD-low and TS-high; colorectal adenocarcinoma, DPD- and TP-low, hepatocellular carcinoma, DPD-high, and TS- and OPRT-low; cholecystic adenocarcinoma, DPD- and TS-high; renal cell carcinoma, DPD-low, and OPRT- and TP-high; urocystic transitional cell carcinoma, DPD-high and OPRT-low; and mammary ductal carcinoma, OPRT-low, and TS- and TP-high. The enzyme expression pattern in cancer tissue was generally similar to that of their normal counterparts. However, TP immunoreactivity in adenocarcinomas of the lung, stomach and gallbladder, and urothelial carcinoma of the urinary bladder was stronger, and DPD immunoreactivity in adenocarcinoma of the breast was weaker, when compared with normal epithelial cells. Non-epithelial cells were also positive for these enzymes. These results indicated that the key enzymes influencing the effects of fluoropyrimidines differ from cancer to cancer. Fluoropyrimidine treatment may be selected, based on the simultaneous immunohistochemical evaluation of the fluoropyrimidine metabolic enzymes.

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Kamoshida S, Shiogama K, Shimomura R, Inada KI, Sakurai Y, Ochiai M et al. Immunohistochemical demonstration of fluoropyrimidine-metabolizing enzymes in various types of cancer. Oncology Reports. 2005 Jan 1;14(5):1223-1230.