COEXPRESSION OF ERYTHROPOIETIN AND VASCULAR ENDOTHELIAL GROWTH-FACTORIN NERVOUS-SYSTEM TUMORS ASSOCIATED WITH VON-HIPPEL-LINDAU TUMOR-SUPPRESSOR GENE LOSS OF FUNCTION

Hemangioblastomas are highly vascular tumors of the central nervous sy stem that overexpress the hypoxia-inducible gene, vascular endothelial growth factor (VEGF), as a consequence of mutational inactivation of the von Hippel-Lindau tumor suppressor gene (VHL). Previous reports sh owed that hemangioblastomas can also express erythropoietin (Epo), whi ch is also hypoxia-inducible. However, Epo expression in hemangioblast omas was observed only in individual cases, and the analyses were main ly based on indirect determination of erythropoiesis-stimulating activ ity. Therefore, we analyzed a series of 11 hemangioblastomas for Epo, VEGF, and VHL expression by Northern blot analysis and compared the re sults with normal brain and glioblastomas. Surprisingly, we observed E po mRMA expression in all hemangioblastoma specimens analyzed, but in none of four glioblastomas, In contrast, VEGF mRNA was expressed in al l hemangioblastomas and all glioblastomas. In situ hybridization revea led neoplastic stromal cells as Epo- and VEGF-producing cells in heman gioblastomas. These results suggest that in the nonhypoxic microenviro nment of hemangioblastoma, Epo, similar to VEGF, might be negatively r egulated by the VHL gene product. (C) 1998 by The American Society of Hematology.