Department of Epidemiology, Second Military Medical University, Shanghai, China.
Cancer. 2011 Sep 15;117(18):4201-11. doi: 10.1002/cncr.26028. Epub 2011 Mar 8.
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.
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.
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 (PTP) 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).
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.
微卫星改变在预测透明细胞肾细胞癌（ccRCC）患者手术切除肿瘤的预后中的作用仍知之甚少。
根据疾病分期，使用 3p、9p 和 14q 染色体上的 12 个标志物对 93 例散发性 ccRCC 患者的标本进行微卫星改变筛查。使用 Kaplan-Meier 方法和 Cox 回归分析评估生存情况。分别使用定量逆转录-聚合酶链反应和免疫组织化学检测靶向基因的表达。
在所筛选的标志物中，D9S168（9p23-22）在标本中的微卫星改变频率最高（36.9%）。D9S168 改变在高分期肿瘤中较为常见。78 例在手术时无远处转移的 ccRCC 患者中位随访 31.7 个月。与无 D9S168 改变的患者相比，D9S168 改变的患者总体生存率和无病生存率较差（P<0.001，对数秩检验）。Cox 回归分析表明，D9S168 改变与癌症相关死亡独立相关（P=0.010）。D9S168 改变位于编码蛋白酪氨酸磷酸酶（PTP）受体 δ（PTPRD）的基因的 5'-非翻译区，与 PTPRD 在信使 RNA 水平的低表达显著相关（P=0.001）。免疫组织化学显示，PTPRD 在正常肾近端管状上皮细胞中的表达较强，而 ccRCC 起源于这些细胞，其在 ccRCC 中表达显著下调（P<0.001；Wilcoxon 秩和检验）。
肿瘤中的 D9S168 微卫星改变预测了接受根治性肾切除术的 ccRCC 患者的不良预后。作者认为 PTPRD 是 ccRCC 中的一个潜在肿瘤抑制基因，具有治疗潜力。
