LOSS OF RETINOBLASTOMA GENE-FUNCTION AND HETEROZYGOSITY AT THE RB LOCUS IN RENAL CORTICAL NEOPLASMS

Alteration of the retinoblastoma (RE) gene, located on chromosome 13q1 4, has been implicated in the pathogenesis and biological behavior of several human cancers. We investigated the RE gene status by Western b lotting and immunohistochemical analysis, as well as loss of heterozyg osity (LOH) at the RE locus in 21 primary human renal neoplasms (inclu ding 3 oncocytomas). In only 1 of 21 tumors was there a discrepancy be tween Western blot and immunochemical staining. Overall, LOH was noted in 6 of 12 informative cases. However, only one of the tumors with LO H at the RE locus had loss of RE protein expression by both Western bl ot and immunohistochemical analysis. Loss of RE function was found in 4 of 18 carcinomas and in none of 3 oncocytomas as determined by absen t RE nuclear staining in tumor cells. LOH at chromosome 13q14 was more noted in high-grade, DNA aneuploid, high-stage tumors and in patients with poor outcome. These results imply that (1) there is likely anoth er tumor-suppressor gene on chromosome 13 involved in renal carcinogen esis, (2) LOH at chromosome 139 loci may be associated with aggressive behavior, and (3) the loss of RE function may have a role in a subset of renal carcinomas. Copyright (C) 1997 by W.B. Saunders Company.