LOSS OF HETEROZYGOSITY OF THE VON-HIPPEL-LINDAU GENE LOCUS IN POLYPOID DYSPLASIA BUT NOT FLAT DYSPLASIA IN ULCERATIVE-COLITIS OR SPORADIC ADENOMAS

Carcinoma in ulcerative colitis (UC) develops from dysplastic precurso r lesions, which include flat dysplasia (FD) and polypoid dysplasias ( PD). PD may present as single or multiple polypoid structures or as pl aque-like lesions that, independent of histological grade, are an indi cation for colectomy. PDs are histologically similar to adenomas and m ay not be readily distinguished by light microscopy. It is not known w hether FD and PD are different entities, or whether they represent eti ologically similar lesions with different morphological expression. We microdissected 25 cases of UC with PD and 19 samples of FD with surro unding chronic colitis (CC) in UC. Loss of heterozygosity (LOH) at the von Hippel Lindau (vHL) gene locus and the putative tumor suppressor genes APC, INK4A (9p16), and p53 was studied. LOH of the vHL gene, INK 4A (9p16), and APC was also studied in 11 sporadic adenomas of the col on. LOH at the vHL locus was present in 50% of the samples of PD and i n 12 ro off the samples of FD. LOH was seen in CC close to PD and FD i n 26% and 12% of cases, respectively. No adenoma showed LOH of the vHL gene markers studied. LOH in p53 was seen in PD in 16% cases and in F D in 42% cases and in CC close to PD and FD in Oro and 14% cases, resp ectively. LOH patterns between PD and FD of the markers for APC and 9p 16 were not different. LOH in APC was seen in two of five cases of ade noma. We conclude that PD and FD share genetic alterations in APC and 9p16 genes. More frequent involvement of the VHL gene in PD and surrou nding CC and involvement of p53 in HGD and CC in FD may represent gene tic differences between the development of PD and FD and may be the ca use of the different morphology. The infrequency of LOH at the vHL loc us in adenomas versus PD may serve as a discriminator between adenomas and PD in diagnostically problematic cases. Copyright (C) 1998 by W.B . Saunders Company.