Clinical & Experimental Metastasis

, Volume 30, Issue 5, pp 607–614 | Cite as

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

  • Sunao Shoji
  • Mayura Nakano
  • Tetsuro Tomonaga
  • Hakushi Kim
  • Kazuya Hanai
  • Yukio Usui
  • Yoshihiro Nagata
  • Masaki Miyazawa
  • Haruhiro Sato
  • Xian Yang Tang
  • Yoshiyuki Robert Osamura
  • Toyoaki Uchida
  • Toshiro Terachi
  • Koichi Takeya
Research Paper


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.


Renal cell carcinoma Metastasis Immunohistochemistry Metastin receptor 



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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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Sunao Shoji
    • 1
  • Mayura Nakano
    • 1
  • Tetsuro Tomonaga
    • 1
  • Hakushi Kim
    • 1
  • Kazuya Hanai
    • 2
  • Yukio Usui
    • 2
  • Yoshihiro Nagata
    • 1
  • Masaki Miyazawa
    • 3
  • Haruhiro Sato
    • 4
  • Xian Yang Tang
    • 5
  • Yoshiyuki Robert Osamura
    • 6
  • Toyoaki Uchida
    • 1
  • Toshiro Terachi
    • 2
  • Koichi Takeya
    • 7
  1. 1.Department of UrologyTokai University Hachioji HospitalHachioji cityJapan
  2. 2.Department of UrologyTokai University School of MedicineIseharaJapan
  3. 3.Department of Obstetrics and GynecologyTokai University School of MedicineIseharaJapan
  4. 4.Department of Internal MedicineTokai University School of MedicineIseharaJapan
  5. 5.Department of PathologyKanagawa Cancer CenterYokohamaJapan
  6. 6.Department of PathologyInternational University of Health and WelfareTochigiJapan
  7. 7.Department of Natural Products and Medical ChemistryTokyo University of Pharmacy and Life Sciences, School of PharmacyHachiojiJapan

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