Expression of the angiogenic factor thymidine phosphorylase in human astrocytic tumors

Thymidine phosphorylase (TP) has been implicated as a potent angiogenic fac tor and a prognostic factor in various human solid tumors. We investigated the expression of TP in a series of human astrocytic tumors using immunohis tochemistry, enzyme-linked immunosorbent assay, and reverse transcriptase/p olymerase chain reaction (RT-PCR) analysis. A total of 63 astrocytic tumors [27 glioblastomas (GBM), 19 anaplastic astrocytomas (AA); 17 low-grade ast rocytomas (LGA)] and 5 normal brain tissues were immunohistochemically stai ned with antibodies to TP, vascular endothelial growth factor (VEGF), p53, MIB-1, and factor-VIII-related antigen. They were also evaluated for the de gree of apoptosis by a ApopTag kit. Ten tumors (5 GBM, 2 AA, 3 LGA) and 3 n ormal brain tissues were: evaluated for their expression of VEGF and TP by RT-PCR analysis. TP was constantly localized in the cytoplasm of astrocytic tumor cells, less intensely in the cytoplasm of vascular endothelial cells , but not in the normal brain. Some of the TP-positive cells were of macrop hage origin, but most positive cells were the tu mor cells themselves. Vasc ular density, MIB-1 positivity, p53 positivity, VEGF expression, and the ap optotic in dex were significantly higher in the TP-positive tumors than in TP-negative tumors. There was a significant correlation between TP and VEGF mRNA expression. In a limited number of glioblastoma cases, the apoptotic index was significantly higher in TP-positive glioblastomas than in TP-nega tive glioblastomas. In human astrocytic tumors, TP was expressed in the tum or, macrophage, and endothelial cells. TP was a potent angiogenic factor cl osely associated with cell proliferation and tumor apoptosis.