Evidence Of Monoclonal And Polyclonal Origin Coexisting For Multifocal Clear Cell Renal Cell Carcinoma

Purpose:Due to the increased use of routine body imaging,the number of incidentally detected tumors has increased and the size of these tumors has decreased. Meanwhile, because of the. excellent clinical outcome and low morbidity of nephron-sparing surgery (NSS) in patients with small tumors and a normal contralateral kidney, NSS has been more and more frequently practised. Nevertheless, the reported incidence of satellite tumor lesions in renal cell carcinoma (5% to 25%) suggests that there be a risk of local recurrence after nephron sparing surgery. But little is known about the biological behavior and malignant potential of these satellite tumors. Therefore, we determined genetic relationships between the multifocal clear cell renal cell tumors by molecular genetic analysis.Materials and Methods:A total of 42 tumors from 20 patients with multifocal clear cell renal cell carcinomas were investigated. All patients had multiple separate clear cell renal carcinomas. Loss of heterozygosity (LOH) analyses were done by polymerase chain reaction (PCR) using 10 markers for chromosome 3p25(D3S1317, D3S1038,D3S1597),3p14 (D3S 1300,D3S1234,D3S1540),7q31(D7S522),8q21(D8S261),9q21(D9S171),and 17p13(TP53).PCR was performed according to standard protocols, followed by gel electrophoresis. The band patterns were observed and analyzed using Labworks3.0.LOH was defined as a>50% reduction of the intensity in either of the two alleles as compared with those in normal control panels. PCRs for each polymorphic microsatellite marker were repeated at least twice from the same DNA preparations and the same results were obtained.Results:Seventeen of the 20 (85%) patients with multifocal clear cell renal cell carcinoma showed allelic loss in at least 1 of 10 microsatellite loci in separate tumors analyzed. Primary and satellite tumors showed a concordant allelic loss pattern in at least 1 informative locus in 14 of the 17 cases. In three of the 14cases, LOH was observed only in satellite tumor lesions, and in two cases, LOH was detected only in primary lesions. A discordant pattern of allelic loss between coexisting kidney tumors was observed in 3 cases.Conclusions:Our data suggest that the majority of multifocal clear cell renal cell carcinomas have a common clonal origin. But we have also detected the evidence for polyclonal origin of multifocal clear cell renal cell carcinoma as well. Consequently, the multifocal clear cell renal cell carcinomas may be classified into monoclonal and polyclonal origin types.