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Pathological function of prostaglandin E2 receptors in transitional cell carcinoma of the upper urinary tract

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Abstract

The prostaglandin E2 receptor, EP4 receptor (EP4R), plays an important role in the development of transitional cell carcinoma of the upper urinary tract (TCC-UUT). However, the clinical significance of other EP receptors (EP1R–3R) is not clear. Furthermore, the pathological function of EP receptors in such patients is not understood. In the present study, we examined the expression of EP1R–3R in 101 TCC-UUT tissues by immunohistochemistry. Furthermore, we defined the relationship between cyclooxygenase (COX)-2 and EP receptor expression, proliferation index (PI), microvessel density (MVD), and expression of metalloproteinase-2 (MMP-2), urokinase-type plasminogen activator (uPA), and exon v6 containing CD44 isoform (CD44 v6) by multivariate analysis. The expression of EP1R, EP2R, and EP3R was positive in 20 (19.8%), 26 (25.7%), and 14 (13.9%) tumor samples, respectively. Expression of these receptors was not associated with pathological findings or survival. COX-2 and EP4R were independently associated with MVD and MMP-2, and uPA or PI and MMP-2, respectively. Other EP receptors were not influenced by any factors. Our results suggest that EP1R–3R play a minimal role in cancer progression in patients with TCC-UUT. On the other hand, EP4R regulates tumor progression via cancer cell proliferation and MMP-2, distinct from COX-2.

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Acknowledgements

We thank Takumi Shimogama and Yoshikazu Tsuji for excellent assistance. This study was supported by in part by grant no. 17791080 from the Japanese Society of the Promotion of Science to Y. Miyata. This study did not receive any funding from any commercial source.

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Authors and Affiliations

  1. Department of Urology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Yasuyoshi Miyata, Kojiro Ohba, Koichiro Nomata, Jiro Eguchi & Hiroshi Kanetake

  2. Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Science, 1-12-4 Sakamoto, Nagasaki, 852-8501, Japan

    Shigeru Kanda

  3. Department of Pathology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Tomayoshi Hayashi

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  1. Yasuyoshi Miyata
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  2. Kojiro Ohba
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  7. Hiroshi Kanetake
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Correspondence to Yasuyoshi Miyata.

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This study was not funded by any commercial organization. It was supported in part by a Grant-in-Aid from the Japanese Society of the Promotion of Science.

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Miyata, Y., Ohba, K., Kanda, S. et al. Pathological function of prostaglandin E2 receptors in transitional cell carcinoma of the upper urinary tract. Virchows Arch 448, 822–829 (2006). https://doi.org/10.1007/s00428-006-0198-1

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  • DOI: https://doi.org/10.1007/s00428-006-0198-1

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