Hughson M D, Schmidt L, Zbar B, Daugherty S, Meloni A M, Silva F G, Sandberg A A
Department of Veterans Affairs Medical Center, Northport, NY 11768-2290, USA.
J Am Soc Nephrol. 1996 Nov;7(11):2461-8. doi: 10.1681/ASN.V7112461.
Renal cell carcinomas (RCC) are responsible for the deaths of 3% to 4% of patients with ESRD. The clear cell carcinoma of the kidney, which comprises 80% of sporadic RCC within the general population, shows a deletion of gene sequences in the short arm of chromosome 3 (3p) in as many as 100% of cases. The von Hippel-Lindau tumor suppressor gene at 3p25-26 is found to be mutated in the nondeleted allele in 57% of these sporadic clear cell carcinomas. This study was undertaken to determine the histopathologic types of RCC occurring in ESRD patients in the United States and to investigate the frequency with which 3p genetic changes can be found in these ESRD tumors. Seventeen end-stage kidneys containing RCC were collected from 15 ESRD patients at ten US medical centers. The tumors were classified by Thoenes' histopathologic typing. DNA extracted from paraffin blocks of tumor and nontumorous tissue was analyzed by single-stranded conformational polymorphism analysis for von Hippel-Lindau mutations and by microsatellite amplification for deletion of 3p gene sequences. Twenty-one RCC were identified in the 18 kidneys. The 21 RCC were classified histopathologically as follows: clear cell, compact, three cases; chromophilic, tubulopapillary, 15 cases; chromophilic, compact, three cases. Among the three clear cell carcinomas, one showed 3p genetic loss. None of the chromophilic RCC showed a 3p deletion and none of 19 tumors studied by single-stranded conformational polymorphism analysis disclosed von Hippel-Lindau mutations. In contrast to the general population, clear cell RCC with 3p abnormalities represent only a small proportion of the renal carcinomas in this collection of ESRD tumors. The findings indicate that the genetic changes underlying the development of most ESRD tumors are different from those occurring in sporadic clear cell RCC and do not characteristically involve the inactivation of a 3p tumor suppressor gene.
肾细胞癌（RCC）导致3%至4%的终末期肾病（ESRD）患者死亡。肾透明细胞癌占普通人群中散发性RCC的80%，在多达100%的病例中显示3号染色体短臂（3p）上的基因序列缺失。在这些散发性透明细胞癌中，57%的未缺失等位基因中发现位于3p25 - 26的冯·希佩尔-林道肿瘤抑制基因发生突变。本研究旨在确定美国ESRD患者中发生的RCC的组织病理学类型，并调查在这些ESRD肿瘤中可发现3p基因变化的频率。从美国十个医疗中心的15名ESRD患者中收集了17个含有RCC的终末期肾脏。肿瘤通过托内斯组织病理学分型进行分类。从肿瘤和非肿瘤组织的石蜡块中提取的DNA通过单链构象多态性分析检测冯·希佩尔-林道突变，并通过微卫星扩增检测3p基因序列的缺失。在18个肾脏中鉴定出21个RCC。这21个RCC的组织病理学分类如下：透明细胞、致密型，3例；嗜色性、肾小管乳头状，15例；嗜色性、致密型，3例。在3例透明细胞癌中，1例显示3p基因缺失。嗜色性RCC均未显示3p缺失，通过单链构象多态性分析研究的19个肿瘤均未发现冯·希佩尔-林道突变。与普通人群相比，具有3p异常的透明细胞RCC在这组ESRD肿瘤中的肾癌中仅占一小部分。研究结果表明，大多数ESRD肿瘤发生发展的潜在基因变化与散发性透明细胞RCC不同，且通常不涉及3p肿瘤抑制基因的失活。
