Correlations between clinical laboratory parameters and angiogenesis and fibrosis markers in myomectomy surgery

Introduction. The search for the relationships between clinical features of patients with uterine fibroids (uterine myoma, leiomyoma) and the characteristics of their myomatous nodules is relevant for identifying prognostic markers. Aim. In patients of reproductive age with uterine fibroids, to identify the presence of correlations between clinical laboratory parameters and markers of inflammation and fibrosis in the surgical specimens. Materials and methods. Myomectomy was performed in 226 female patients with myomatous no¬dules. Examination of patients included clinical investigations (ultrasound, magnetic resonance imaging), extragenital abnormalities were assessed. Samples of the dominant myomatous nodules and myometrium were examined using enzyme-linked immunosorbent assay (ELISA) for the content of baseline and stimulated by polyclonal activators (PA) vascular endothelial growth factor (VEGF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the incubation medium. The expression of progesterone receptors (PgR) and VEGF using immunohistochemistry (IHC) was assessed. Results. The combination of uterine fibroids with endometriosis in reproductive-aged women influenced a number of histological and molecular characteristics of the dominant myomatous nodule: positively – on the grade of fibrosis (p < 0.0001), negatively – on the PA-induced production of GM-CSF and VEGF (p = 0.0054 and p = 0.0016, respectively). Patients with adenomyosis had more myomatous nodules (p = 0.0192) compared with patients without any form of endometriosis, while the largest nodule diameter and the degree of fibrosis were in women without adenomyosis (p = 0.0397 and p = 0.0344, respectively). PA-induced VEGF production in the nodule is greater in adenomyosis (p = 0.0326), while PgR expression in the perifocal myometrium is less (p = 0.045). In patients with uterine myoma, the body mass index had a weak positive correlation with VEGF expression in the perifocal myometrium. The number of myomatous nodules had weak positive correlation with the stimulation index of PA (SIPA) which reflects their influence of the VEGF production in the dominant nodule in vitro. The degree of fibrosis of the dominant nodule was characterized by moderately positive correlation with the expression of VEGF in the perifocal myometrium according to IHC. Conclusion. The results of the study reflect the systemic nature of myomatous transformation with multifocal myometrium tumor growth and the potential for the formation of new myomatous nodules, especially in women with elevated body mass index.