RENAL-CELL CARCINOMA OF END-STAGE RENAL-DISEASE - A HISTOPATHOLOGIC AND MOLECULAR-GENETIC STUDY

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 d eletion 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 thes e sporadic clear cell carcinomas. This study was undertaken to determi ne the histopathologic types of RCC occurring in ESRD patients in the United States and to investigate the frequency with which 3p genetic c hanges 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 w as analyzed by single-stranded conformational polymorphism analysis fo r von Hippel-Lindau mutations and by microsatellite amplification for deletion of 3p gene sequences. Twenty-one RCC were identified in the 1 8 kidneys, The 21 RCC were classified histopathologically as follows: clear cell, compact, three cases; chromophilic, tubulopapillary, 15 ca ses; chromophilic, compact, three cases. Among the three clear cell ca rcinomas, one showed 3p genetic loss, None of the chromophilic RCC sho wed a 3p deletion and none of 19 tumors studied by single-stranded con formational polymorphism analysis disclosed von Hippel-Lindau mutation s. In contrast to the general population, clear cell RCC with 3p abnor malities 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 characteris tically involve the inactivation of a 3p tumor suppressor gene.