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.