HMB-45 AND TUBERIN IN HAMARTOMAS ASSOCIATED WITH TUBEROUS SCLEROSIS

Tuberous sclerosis (TSC) is an autosomal dominant condition characteri zed by various hamartomas. To assess whether these hamartomas have com mon features, we immunohistochemically analyzed an autopsy case of TSC with subependymal giant cell astrocytoma, hamartomatous lymphangiolei omyomatosis in the lungs and uterus, and angiomyolipomas in the liver, bilateral kidneys, parametrium, and a lymph node, using the specific antibodies for tuberin (the gene product of TSC2) and HMB-45 (a monocl onal antibody specific for human melanoma). Tuberin was ubiquitously e xpressed in the normal organs, It was negative or very weakly expresse d in the hamartomas, In contrast, HMB-45 was commonly observed in the hamartomas except for the lesions in the brain. The subependymal giant cell astrocytoma was composed of cells immunoreactive for synaptophys in, neurofilament protein, glial fibrillary acidic protein, and S-100 protein but negative for HMB-45 and tuberin. The suppression of tuberi n in the brain tumor and visceral hamartomas and an abnormal expressio n of HMB-45 in the visceral hamartomas were observed. We conclude that the hamartomas associated with TSC have common phenotypic and etiolog ic expressions and that the genes responsible for both tuberin and the antigen recognized by HMB-45 have important roles in the pathogenesis of these hamartomas.