Prognostic significance of dihydropyrimidine dehydrogenase expression in breast cancer

Horiguchi, Jun; Takei, Hiroyuki; Koibuchi, Yukio; Iijima, Kotaro; Ninomiya, Jun; Uchida, Kazumi; Ochiai, Ryosuke; Yoshida, Miho; Yokoe, Takao; Iino, Yuichi; Morishita, Yasuo

doi:10.1038/sj.bjc.6600040

Cited by 26 publications

(17 citation statements)

References 8 publications

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“…Half of the breast and gastric cancer tissues lacked DPD expression. A similar immunohistochemical finding was shown in breast cancers by Horiguchi et al [9]. In our study, eight of nine poorly differentiated adenocarcinomas of the stomach were negative for DPD.…”

Section: Discussionsupporting

confidence: 71%

“…Significant correlation between the immunohistochemical DPD expression and the 5-FU resistance or poor prognosis has been demonstrated in pulmonary, mammary, and oral carcinomas [9,10,15,22]. Nozawa et al reported that DPD expression in gastric carcinoma was comparable between the biopsy samples and resected surgical specimens [23].…”

Section: Introductionmentioning

confidence: 99%

“…Immunohistochemical analysis of DPD has been performed in a limited number of studies [9,10,15,22,23,29]. Significant correlation between the immunohistochemical DPD expression and the 5-FU resistance or poor prognosis has been demonstrated in pulmonary, mammary, and oral carcinomas [9,10,15,22].…”

Section: Introductionmentioning

confidence: 99%

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Immunohistochemical Demonstration of Dihydropyrimidine Dehydrogenase in Normal and Cancerous Tissues

Kamoshida

Shiogama

Matsuoka

et al. 2003

Acta Histochem. Cytochem.

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Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU). Previous studies have suggested that high enzyme activities and mRNA levels of DPD are involved in the resistance of cancers to 5-FU. For immunohistochemically demonstrating the tumor resistance to 5-FU, we determined the most suitable and reproducible condition of antigen retrieval for DPD localization in formalin-fixed, paraffin-embedded sections, and analyzed DPD expression in various types of normal and cancerous tissues. Pressure cooking in ethylenediaminetetraacetic acid, pH 8.0, was the best choice for retrieving the antigenicity of DPD. In normal tissues, DPD immunoreactivity was consistently detected in squamous epithelia, hepatocytes, Clara cells, ductal/glandular epithelia of various organs, myoepithelial cells, and non-epithelial cells such as macrophages, plasma cells, and part of the endothelial cells and fibroblasts. DPD was strongly expressed in adenocarcinomas of the lung, gallbladder and pancreas, hepatocellular carcinomas, and transitional cell carcinomas of the urinary bladder. Squamous cell carcinomas of the pharynx and lung were moderately reactive. Carcinomas of the breast and stomach revealed less consistent and less intense reactivity. Colorectal adenocarcinomas were not immunoreactive. The polyclonal antibody gave a broader and stronger reactivity than the monoclonal antibody KM1915, particularly in the normal epidermis and skin appendage as well as in squamous cell carcinomas and gastric cancers. The present results hopefully contribute to further investigations, in which the immunohistochemical demonstration of DPD is utilized as a tool of tailor-made chemotherapy for selecting of patients with cancer resistant to 5-FU and its derivatives.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

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Immunohistochemical Demonstration of Dihydropyrimidine Dehydrogenase in Normal and Cancerous Tissues

Kamoshida

Shiogama

Matsuoka

et al. 2003

Acta Histochem. Cytochem.

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“…Both of these proteins have been implicated in metastatic spread of breast cancer. Besides mdr-1 expression, we examined dihydropyrimidine dehydrogenase (DPD) since DPD-positive tumors have been found to be prognostic of poor survival [59]. Similarly, expression of COX-2 is predictive of poor survival [60].…”

Section: The Role Of Pkc-α In Breast Cancermentioning

confidence: 99%

Protein Kinase C Alpha Expression in Breast and Ovarian Cancer

Lahn¹,

Köhler

Sundell³

et al. 2004

Oncology

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In recent years research has focused on the development of specific, targeted drugs to treat cancer. One approach has been to block intracellular signaling proteins, such as protein kinase C alpha (PKC-α). To help support the rationale for clinical studies of a PKC-α-targeted therapy in breast and ovarian cancers, we reviewed publications studying PKC-α expression in these tumors. Since these investigations were mostly performed in cell lines, we supplemented this review with some preliminary findings from studies examining PKC-α expression in tumor tissue biopsies obtained from patients with breast and ovarian cancer. Based on the reviewed publications using representative cell lines and our preliminary findings on tumor tissue of patients with breast cancer, we infer that PKC-α levels may especially be increased in breast cancer patients with low or negative estrogen receptor (ER) levels. Thus, clinical studies determining efficacy of selective or specific inhibitors of PKC-α should include determination of ER status in order to help answer whether blocking PKC-α in patients with low or absent ER can result in clinical benefit.

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“…In contrast, high DPD expression in many tumors is correlated with resistance to 5-FU. [34][35][36] Moreover, DPD expression is often associated with tumor aggressiveness or poor outcome in some cancers. [34][35][36] Takabayashi …”

Section: Discussionmentioning

confidence: 99%

Expression of thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyl transferase in prostate cancer

Miyoshi

Uemura

Ishiguro

et al. 2005

Prostate Cancer Prostatic Dis

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The enzymes thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyl transferase (OPRT) are involved in the metabolism of the anticancer drug 5-fluorouracil. No reports have examined the expression of these enzymes in prostate cancer (CaP). A total of 25 previously untreated, hormone-sensitive CaP tissue samples and 11 benign prostatic hyperplasia (BPH) specimens were examined. Tissue of CaP and BPH tissue samples were obtained from formalin-fixed, paraffin-embedded sections by laser-captured microdissection, and then RNA was extracted. mRNA expression of TS, DPD, TP, and OPRT was analyzed by quantitative reverse transcriptase-polymerase chain reaction. TS and OPRT expression levels were significantly higher in CaP samples than in BPH. DPD expression level in poorly differentiated CaP was significantly lower than that in CaP with more favorable-well or moderately differentiated-histopathology.

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Prognostic significance of dihydropyrimidine dehydrogenase expression in breast cancer

Cited by 26 publications

References 8 publications

Immunohistochemical Demonstration of Dihydropyrimidine Dehydrogenase in Normal and Cancerous Tissues

Immunohistochemical Demonstration of Dihydropyrimidine Dehydrogenase in Normal and Cancerous Tissues

Protein Kinase C Alpha Expression in Breast and Ovarian Cancer

Expression of thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyl transferase in prostate cancer

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