title: Value of metastin receptor immunohistochemistry in predicting metastasis after radical nephrectomy for pT1 clear cell renal cell carcinoma.
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.
authors.affiliation: Department of Urology, Tokai University Hachioji Hospital, 1838 Ishikawa-machi, Hachioji city, Tokyo, 192-0032, Japan. sunashoj@mail.goo.ne.jp
authors.forename: Sunao
authors.initials: S
authors.lastname: Shoji
authors.forename: Mayura
authors.initials: M
authors.lastname: Nakano
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Tomonaga
authors.forename: Hakushi
authors.initials: H
authors.lastname: Kim
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hanai
authors.forename: Yukio
authors.initials: Y
authors.lastname: Usui
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nagata
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyazawa
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Sato
authors.forename: Xian Yang
authors.initials: XY
authors.lastname: Tang
authors.forename: Yoshiyuki Robert
authors.initials: YR
authors.lastname: Osamura
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Uchida
authors.forename: Toshiro
authors.initials: T
authors.lastname: Terachi
authors.forename: Koichi
authors.initials: K
authors.lastname: Takeya
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy / Q000379:methods*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D000074502:Receptors, Kisspeptin-1
chemical_list: D014408:Biomarkers, Tumor; C118688:KISS1R protein, human; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1