Clear-cell and papillary carcinoma of the kidney: an analysis of chromosome 3, 7, and 17 abnormalities by microsatellite amplification, cytogenetics, and fluorescence in situ hybridization.

Clear-cell and papillary renal cell carcinomas (RCCs) have specific genetic changes that allow them to be classified on the basis of histopathology and on the basis of cytogenetic and molecular genetic findings. Clear-cell carcinomas are characterized by a deletion of gene sequences on the short arm of chromosome 3 (3p). Papillary RCCs do not have 3p deletions but have an increase in chromosomal number that usually includes trisomies of chromosomes 7 and 17. This study was undertaken to determine whether PCR-amplified DNA microsatellites can be used to detect numerical abnormalities of chromosomes 7 and 17 and whether the numerical abnormalities and 3p deletions that are detected by microsatellite analysis can be correlated with histopathologic tumor types. A series of histologically unambiguous RCCs consisting of three papillary and ten clear-cell RCCs were studied by cytogenetics and by fluorescence in situ hybridization (FISH) with chromosome 7 and 17 centromeric probes. Microsatellites on the long and short arms of chromosomes 3, 7, and 17 were amplified in paired normal tissue and tumor samples, and the reaction products were analyzed for differences between the normal and the tumor allele ratios. Clear-cell carcinomas showed loss of heterozygosity (LOH) of 3p but not 3q alleles in eight of ten cases. LOH of 3p and 3q was seen in one case of papillary RCC that cytogenetically had two normal chromosomes 3. This indicated a nondisjunction duplication that could be confused with monosomy 3 if only microsatellite studies were performed. Differences in microsatellite allele ratios between normal tissue and tumor correlated with the presence of trisomy 7 that was identified in clear-cell and papillary RCCs by cytogenetics and by FISH. Microsatellite analysis did not detect numerical chromosome 17 abnormalities in the papillary RCCs but did show an abnormality in one clear-cell carcinoma that was markedly aneusomic for chromosomes 7 and 17 by FISH. In this collection of cases, microsatellite amplification genetically distinguished only clear-cell RCCs showing 3p but not 3q LOH as a separate class of tumors. The method detected abnormalities in chromosome number that were found in both clear-cell and papillary RCCs.