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Value of metastin receptor immunohistochemistry in predicting metastasis after radical nephrectomy for pT1 clear cell renal cell carcinoma

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Abstract

KISS-1 is a metastasis-suppressor gene of human melanoma, and encodes metastin, which was identified as the ligand of a G-protein-coupled receptor (metastin receptor). The precursor protein is cleaved to 54 amino acids, which may be further truncated into carboxy-terminal fragments. Previous studies showed that lack of metastin receptor in clear cell renal cell carcinoma (RCC) is associated with tumor progression, but the prediction of metastasis in patients with pT1 clear cell RCC after radical nephrectomy is difficult. The objective of this study was to evaluate the usefulness of metastin receptor immunohistochemistry in predicting metastasis after nephrectomy for pT1 clear cell RCC. After verification of the correlation between immunostaining and mRNA expression, we evaluated the clinical value of metastin receptor immunohistochemistry. Fifty-four patients were enrolled in this study; following radical nephrectomy, seven patients were found to have lung metastasis. The sensitivity, specificity, positive predictive value, and negative predictive value with negative immunostaining of metastin receptor were 85.7, 97.6, 46.2, and 97.6 %, respectively. Metastasis-free survival rates were significantly higher in patients with positive staining (97.6 %) than in patients with negative staining (53.8 %) (P < 0.001). In univariate analysis for metastasis-free survival, negative immunostaining of metastin receptor was a significant risk factor for metastasis (P = 0.001). Furthermore, negative immunostaining of metastin receptor was an independent predictor for metastasis in multivariate analysis (hazard ratio, 3.735; 95 % CI 0.629–22.174; P = 0.002). In conclusion, our study suggests that negative expression of metastin receptor in clear cell RCC is significantly related to metastasis.

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Acknowledgments

The authors would like to sincerely express their appreciation to Norihide Mochizuki and Tomohisa Machida for their technical assistance in the immunohistochemistry studies.

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Authors and Affiliations

  1. Department of Urology, Tokai University Hachioji Hospital, 1838 Ishikawa-machi, Hachioji city, Tokyo, 192-0032, Japan

    Sunao Shoji, Mayura Nakano, Tetsuro Tomonaga, Hakushi Kim, Yoshihiro Nagata & Toyoaki Uchida

  2. Department of Urology, Tokai University School of Medicine, Isehara, Japan

    Kazuya Hanai, Yukio Usui & Toshiro Terachi

  3. Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Japan

    Masaki Miyazawa

  4. Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan

    Haruhiro Sato

  5. Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan

    Xian Yang Tang

  6. Department of Pathology, International University of Health and Welfare, Tochigi, Japan

    Yoshiyuki Robert Osamura

  7. Department of Natural Products and Medical Chemistry, Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Hachioji, Japan

    Koichi Takeya

Authors
  1. Sunao Shoji
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  2. Mayura Nakano
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  3. Tetsuro Tomonaga
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  4. Hakushi Kim
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  5. Kazuya Hanai
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  7. Yoshihiro Nagata
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  8. Masaki Miyazawa
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  9. Haruhiro Sato
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  10. Xian Yang Tang
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  11. Yoshiyuki Robert Osamura
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  12. Toyoaki Uchida
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  13. Toshiro Terachi
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  14. Koichi Takeya
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Correspondence to Sunao Shoji.

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Shoji, S., Nakano, M., Tomonaga, T. et al. Value of metastin receptor immunohistochemistry in predicting metastasis after radical nephrectomy for pT1 clear cell renal cell carcinoma. Clin Exp Metastasis 30, 607–614 (2013). https://doi.org/10.1007/s10585-012-9564-3

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  • DOI: https://doi.org/10.1007/s10585-012-9564-3

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