INTRATUMORAL HETEROGENEITY OF VON-HIPPEL-LINDAU GENE DELETIONS IN RENAL-CELL CARCINOMA DETECTED BY FLUORESCENCE IN-SITU HYBRIDIZATION

Although chromosome 3p deletions are considered an initial event in cl ear cell renal cell carcinoma (RCC), the reported prevalence of 3p del etions is highly variable. Because molecular analyses may be influence d by intratumoral heterogeneity, this study was performed to evaluate the genetic heterogeneity of the von Hippel-Lindau (VAL) gene (on 3p25 .5) in BCC. Fifty-three clear cell and papillary RCCs were examined by dual-labeling fluorescence in situ hybridization with probes for the VHL gene and chromosome 3 centromere. The results were compared with h istopathological phenotype, proliferative activity (Ki-67 labeling ind ex) and 8p/17p deletions (both suggested to be linked to RCC progressi on), A clear-cut VHL deletion tin more than 40% of cells) was detectab le in 69% of clear cell RCCs but was not detectable in nine papillary RCCs. A considerable genetic heterogeneity of VHL deletions was seen i n clear cell RCCs including VHL-deleted subpopulations with different chromosome 3 counts within individual tumors as well as populations wi th and without VHL deletions. 8p22 and 17p13 deletions teach of which were detected in 18% of clear cell RCCs) were both linked to VHL delet ions. However, sp and 17p deletions were not associated with tumor gra de, stage, or Ki-67 labeling index, The data indicate that some clear cell RCCs may develop independently of VHL alterations.