Optimization of Therapy Tactics in Patients with Endometrial Hyperplastic Prosesses

Abstract

Study Objective: The recent developments in molecular genetics have shown that mechanisms regulating proliferation, differentiation, transformation, apoptosis and elimination of epithelial cells form the basis for maintanance of endometrial intactness and function.Design: Prospective study. The study was performed by immunohistochemical analysis (markers p53, p27, Ki67 and cyclin E as well as steroid hormone receptors expression) using 44 patients in premenopausal age.Setting: The aim of the study: to improve diagnostic and therapy practice in patients with endometrial hyperplasy (EH).Patients: N/AIntervention: The endometrial tissue was obtained in D&C with the hysteroscopic control/Measurements and Main Results: In patients with polyps and EH without atypia mt p53 has not been found, however gene mutant products expression was discovered in more than one third of patients with atypical EH (40%). The level of proliferation marker Ki67 in all the samples studied, was raised, but the most high values were detected in bioptates of EH with atypia (23.3% of tagged nuclei in glandular epithelium cells and 11.3% in stromal cells). Expression of estrogen end progesterone receptors was significantly higher (284.14±4.53 and 262.22±6.42 respectively) in glandular without atypia and glandular-cystic EH (110.41±3.55 and 142.69±4.09 respectively). Higher activity of cyclin E (95.0±3.7 in cytoplasma and 30.0±7.3 in endometrial cell nuclei) and low contents of cell cycle protein-inhibitor p27 (39.4±8.1 in cytoplasma and 19.3±8.6 in endometrial cell nuclei) were revealed in endometrial samplings of patients with atypical EH, comparing to patients with polyps and EH without atypia.Conclusion: The estimation of steroid hormone receptors expression, apoptosis and proliferation markers and cell cycle regulators contributes to establishing groups of risk for EH development as well as therapy and management tactics optimization taking into consideration molecular-cellular determinants (rational hormonal therapy, both of apoptosis inductors and antiproliferative agents prescription, and operative treatment in some cases). Study Objective: The recent developments in molecular genetics have shown that mechanisms regulating proliferation, differentiation, transformation, apoptosis and elimination of epithelial cells form the basis for maintanance of endometrial intactness and function. Design: Prospective study. The study was performed by immunohistochemical analysis (markers p53, p27, Ki67 and cyclin E as well as steroid hormone receptors expression) using 44 patients in premenopausal age. Setting: The aim of the study: to improve diagnostic and therapy practice in patients with endometrial hyperplasy (EH). Patients: N/A Intervention: The endometrial tissue was obtained in D&C with the hysteroscopic control/ Measurements and Main Results: In patients with polyps and EH without atypia mt p53 has not been found, however gene mutant products expression was discovered in more than one third of patients with atypical EH (40%). The level of proliferation marker Ki67 in all the samples studied, was raised, but the most high values were detected in bioptates of EH with atypia (23.3% of tagged nuclei in glandular epithelium cells and 11.3% in stromal cells). Expression of estrogen end progesterone receptors was significantly higher (284.14±4.53 and 262.22±6.42 respectively) in glandular without atypia and glandular-cystic EH (110.41±3.55 and 142.69±4.09 respectively). Higher activity of cyclin E (95.0±3.7 in cytoplasma and 30.0±7.3 in endometrial cell nuclei) and low contents of cell cycle protein-inhibitor p27 (39.4±8.1 in cytoplasma and 19.3±8.6 in endometrial cell nuclei) were revealed in endometrial samplings of patients with atypical EH, comparing to patients with polyps and EH without atypia. Conclusion: The estimation of steroid hormone receptors expression, apoptosis and proliferation markers and cell cycle regulators contributes to establishing groups of risk for EH development as well as therapy and management tactics optimization taking into consideration molecular-cellular determinants (rational hormonal therapy, both of apoptosis inductors and antiproliferative agents prescription, and operative treatment in some cases).