D9S168 Microsatellite Alteration Predicts a Poor Prognosis in Patients With Clear Cell Renal Cell Carcinoma and Correlates With the Down-Regulation of Protein Tyrosine Phosphatase Receptor Delta

BACKGROUND: The role of microsatellite alterations in surgically excised tumors in predicting the prognosis of patients with clear cell renal cell carcinoma (ccRCC) remains largely unknown. METHODS: Specimens from 93 patients with sporadic ccRCC were used to screen microsatellite alterations using 12 markers on chromosomes 3p, 9p, and 14q according to disease stage. Survival was evaluated by using the Kaplan-Meier method and Cox regression analysis. The expression of targeted genes was examined using quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. RESULTS: Of the markers that were screened, D9S168 (9p23-22) had the highest frequency (36.9%) of microsatellite alteration in the specimens. D9S168 alterations were frequent in high-stage tumors. Seventy-eight patients who had ccRCC without distant metastasis at the time of surgery were followed for a median of 31.7 months. Overall survival and disease-free survival were poorer for patients with D9S168 alteration than for those without alteration (P < .001 for each; log-rank test). Cox regression analysis indicated that D9S168 alteration was associated independently with cancer-related death (P = .010). The D9S168 alteration, which was located at the 5'-untranslated region of a gene that encodes protein tyrosine phosphatase (PIP) receptor delta (PTPRD), was associated significantly with low expression of PTPRD at the messenger RNA level (P = .001). Immunohistochemistry revealed that the expression of PTPRD was strong in normal kidney proximal tubular epithelial cells, from which ccRCC originated, and was greatly down-regulated in ccRCC (P < .001; Wilcoxon rank-sum test). CONCLUSIONS: D9S168 microsatellite alteration in tumors predicted a poor prognosis for patients with ccRCC after curative nephrectomy. The authors concluded that PTPRD is a putative tumor suppressor in ccRCC and has therapeutic potential. Cancer 2011;117:4201-11. (C) 2011 American Cancer Society.