The aim of this study was to investigate the relationship between the expression of vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-beta 1 and TGF-beta 3), and hypoxia inducible factor 1 alpha (HIF-1 alpha) in gestational trophoblastic diseases to highlight the possible histogenesis. Twenty-one partial hydatidiform moles (PHM), 19 complete hydatidiform moles (CHM), 13 choriocarcinomas, and 20 nonhydropic spontaneous abortions (control group) were evaluated with immunohistochemistry using VEGF, HIF-1 alpha TGF beta 1, and TGF beta 3. The extent of immunohistochemical positivity (0% = 0, 1-24% = 1, 25-49% = 2, 50-74% = 3, and greater than 75% = 4) and intensity (no staining = 0, weak staining = 1, medium staining = 2, and strong staining = 3) were recorded. The expression of VEGF in spontaneous abortions and choriocarcinoma was higher than the expression in PHM and CHM. HIF-1 alpha was strongly expressed in the choriocarcinomas compared to the other subgroups. Nonhydropic spontaneous abortions (control group) showed the highest TGF beta 1 expression levels among the case subgroups, followed by PHM, CHM, and choriocarcinoma (p<0.001). The expression of TGF beta 3 was seen in all groups, but the highest level of expression was observed in both CHM and choriocarcinoma. We conclude that higher levels of VEGF, HIF-1 alpha and TGF beta 3 expression in choriocarcinoma might be involved in the development of trophoblastic diseases. (C) 2009 Elsevier GmbH. All rights reserved.