GENETIC ALTERATIONS AND EPITHELIAL DYSPLASIA IN JUVENILE POLYPOSIS SYNDROME AND SPORADIC JUVENILE POLYPS

Juvenile polyps are regarded as hamartomatous polyps and occur in spor adic and familial syndromic settings. There is increased risk of gastr ointestinal neoplasia in patients with juvenile polyposis syndrome, bu t the molecular mechanisms are not known. We therefore studied 78 colo rectal juvenile polyps from 12 patients with juvenile polyposis syndro me and 34 sporadic juvenile polyps for epithelial dysplasia and geneti c changes associated with colorectal neoplasia. Dysplasia occurred in 31% of syndromic juvenile polyps but not in sporadic juvenile polyps ( P < 0.0001). Topographic control of proliferation and expression of th e cyclin-dependent kinase inhibitor p21((WAF1/CIP1)) seen in native co lorectal epithelium was lost in 79% of dysplastic juvenile polyps and in 8% of nondysplastic juvenile polyps (P < 0.000001). Somatic mutatio ns in the adenomatous polyposis coli (APC) gene were demonstrated in 5 0% of dysplastic juvenile polyps (3 of 6) but not in any of 16 juvenil e polyps without dysplasia (P = 0.01). Both sporadic and syndromic dro mic juvenile polyps had K-ras mutations (14%) and there was no relatio nship to dysplasia. p53 gene product overexpression identified by immu nohistochemical staining occurred rarely in dysplastic juvenile polyps (2 of 24, 8%). Our results indicate that the multiple genetic alterat ions involved in usual colorectal neoplasia also play a role in neopla stic transformation of juvenile polyps, predominantly in juvenile poly posis syndrome.