Human heparanase has been shown to function in tumor progression, metastatic spread, and tumor angiogenesis. The aim of the present study was to assess heparanase expression in endometrial cancer in correlation with neovascularization and clinicopathological factors. Forty endometrial cancers were obtained from previously untreated patients (median age 55.5, range 33-78 years). The expression of heparanase mRNA was evaluated using a semiquantitative reverse transcriptase-polymerase chain reaction. Tumor angiogenesis was assessed using microvessel counting. The Mann-Whitney U test, one-factor ANOVA test, and Spearman's test were used to determine the relationship between heparanase expression, microvessel density, and clinicopathological parameters. The expression of heparanase mRNA was detected in 20 of 40 (50%) endometrial cancers, and was significantly correlated with FIGO stage IIIc (p = 0.0075), the presence of lymph-vascular space involvement (p = 0.0041), lymph node metastasis (p = 0.0049), and histological tumor grade (p = 0.0030). Microvessel density was also associated with FIGO stage IIIc (p = 0.027), the presence of lymph-vascular space involvement (p = 0.001), lymph node metastasis (p = 0.038), ovarian metastasis (p = 0.030) and histological tumor grade (p = 0.0030). Moreover, we found a strong positive correlation between heparanase expression and microvessel density (r(2) = 0.475, p = 0.0001). These results suggest that the expression of heparanase may influence different malignant behaviors in endometrial cancer. Copyright (C) 2003 S. Karger AG, Basel.