Abstract
This case-control study aimed to investigate the expression of natural killer cells (NKCs) and the integrated optical density (IOD) of vascular endothelial growth factor (VEGF) and to quantify microvascular density (MVD) in endometrial biopsies from women with endometrial hyperplasia (EH) relative to normal subjects. Histological data from four groups were analyzed. The study population included 30 women with simple EH without atypia, 25 patients with complex EH without atypia, 25 with complex EH with atypia and 25 healthy women with non-hyperplastic endometrium (control group). Paraffin sections were immunostained with antibodies against CD56, VEGF-A and CD34 using an Avidin Biotin Peroxidase technique. The evaluation of NKC density and IOD of VEGF expression and measurement of MVD were performed using light microscopy examination and image analysis techniques. Increased numbers of NKCs were documented in cases of complex EH with atypia compared with the other groups (p<0.001). The number of NKCs was lower in cases of hyperplasia without atypia compared with the controls, but the difference was not significant. The IOD of VEGF-A and MVD increased significantly with progression from the non-hyperplastic endometrium through the three groups of EH (p<0.001). We observed a significant correlation between the MVD and the IOD of VEGF-A in the studied groups (r=0.434; p<0.001). Additionally, NKCs density was correlated significantly with IOD of VEGF-A (r=0.661; p<0.001) and with the MVD (r=0.473; p<0.001). These results suggest that NKC-count, IOD of VEGF and endometrial MVD are all related to the histological changes of the endometrium and that endometrial hyperplasia exhibits distinct immunological backgrounds in the context of NKC infiltration and VEGF production.