Markers of proliferation and angiogenesis in endometrial hyperplastic processes combined with uterine fibroids

Abstract

Aim. To evaluate the levels of proliferation marker Ki-67 and vascular endothelial growth factor-A (VEGF-A) in the serum of women with various forms of endometrial hyperplastic processes (EHP) in combination with uterine fibroids and their relationship with clinical and anamnestic features. Materials and methods. A total of 107 patients with various forms of EHP and endometrial adenocarcinoma were examined at the gynecological department of Zaporizhzhia City Clinical Hospital No. 7 and CI “Zaporizhzhia Regional Clinical Oncology Dispensary” of the ZRC. The first group included 34 patients with simple endometrial hyperplasia without atypia (SHWA) (mean age 41.60 ± 1.31 years). The second group consisted of 47 patients with complex endometrial hyperplasia without atypia (CHWA) (mean age 40.90 ± 1.34 years). Groups were divided into subgroups depending on the presence of uterine fibroids. The third group included 26 patients with endometrial adenocarcinoma (mean age 43.59 ± 1.43 years). The control group consisted of 20 healthy women. The patients underwent ultrasound examination on an apparatus “MyLab50” (“Esaote”, Italy) and video hysteroscopy (“Karl Storz”, Germany). Morphological study of tissue specimens was performed in the Pathology Department of the University Hospital of ZSMU. Serum proliferation marker Ki-67 and VEGF-А levels were determined by enzyme immunoassay using Elabscience reagents (USA). Results. The Ki-67 level analysis revealed an increase in this marker in the CHWA and endometrial adenocarcinoma groups compared with the controls (P < 0.05) and SHWA group (P < 0.05). Women with endometrial adenocarcinoma had significantly higher Ki-67 levels compared to controls (P < 0.05) and SHWA (P < 0.05). Patients with CHWA and adenocarcinoma presented higher levels of serum VEGF-A than the control and SHWA groups. VEGF-A levels were significantly higher in the SHWA and CHWA groups with fibroids compared to patients without fibroids (P < 0.05). A correlation analysis in women with EHP and uterine fibroids revealed a significant positive relationship between Ki-67 level and M-echo thickness, EHP history duration. The level of VEGF-A in patients with EHP and uterine fibroids significantly positively correlated with the myomatous nodule diameter, age and EHP history duration. Conclusions. The CHWA group showed an increase in the level of Ki-67 proliferation marker compared to the SHWA group and healthy women. The level of VEGF-A was significantly increased in order from SHWA to adenocarcinoma and was the highest in women with malignancies. Patients with SHWA and CHWA combined with uterine fibroids had significantly higher VEGF-A levels than those without fibroids.