EXPRESSION PATTERN OF THE VONHIPPEL-LINDAU PROTEIN IN HUMAN TISSUES

von Hippel-Lindau (VHL) disease is an autosomal dominant inherited dis order characterized by extensively vascularized tumors and cysts in sp ecific organs. The VHL gene product plays a critical role in the regul ation of transcription elongation by RNA polymerase II. To provide ins ight into which cells the VHL protein is expressed, we performed immun ohistochemistry on human tissue and tumors. The VHL protein was widely expressed in normal human tissue. The cellular distribution of the pr otein was confined to the cytoplasm of specific cell types. High level s of expression of the protein were observed in neural tissue, especia lly in Purkinje cells, Golgi type II cells, and dentate nucleus of the cerebellum, pontine nuclei, the inferior olivary nucleus of the medul la oblongata, orthosympathetic ganglia, myenteric, and submucous plexu s of the colon. In the other target organs of the VHL disease, high ex pression was observed in the renal tubule system, the exocrine pancrea s, the adrenal cortex, and liver parenchyma. The VHL protein was also expressed in organs not at risk for the disease. The eosinophilic cell s of the pituitary gland, epithelial cells of the follicles of the thy roid, epithelial cells of the intestines, bile ducts, and bronchial ep ithelia showed strong VHL immunoreactivity. Immunohistochemistry did n ot facilitate the discrimination of tumors obtained from VHL patients or tumors unrelated to the VHF disease. Renal cell carcinomas, hemangi oblastomas, and pheochromocytomas, either VHL-related or sporadic, dem onstrated positive staining for the VHL protein, which suggests that t he antibody also recognizes the mutated VHL protein. The present study suggests a role for the VHL gene that goes beyond the organs involved in the disease. The recognition of cell-specific VHL expression provi des a framework for further studies to elucidate the normal function o f the VHL gene and to determine its role in specific cell types.