Проведена оценка пролиферативных и антипролиферативных свойств клеток эндометрия при его гиперплазии, ассоциированной с хроническим эндометритом (ХЭ). В исследование вошли 60 пациенток, из них у 20 при гистологическом изучении биоптатов эндометрия выявлены гиперплазия эндометрия без атипии, ассоциированная с ХЭ (I группа), у 20-ХЭ (II группа) и у 20-нормальный эндометрий (III группа-группа контроля). Установлено, что при гиперплазии эндометрия, ассоциированной с ХЭ, наблюдается повышенная экспрессия Ki-67 (площадь иммунопозитивных структур составила 22.73 ± 2.03 % по сравнению с 7.43 ± 1.05 % в группе хронического эндометрита и 2.0 % в группе контроля) и p16 INK4a (площадь иммунопозитивных структур достигла 30.0 % по сравнению с 5.8 % во II группе и 2.6 % в III группе). Уровень экспрессии p16 INK4a прямо пропорционален уровню экспрессии Ki-67; коэффициент корреляции Спирмена составил 0.869, p = 0.0001, коэффициент Пирсона-0.909, p = 0.0001. Коэкспрессия Ki-67 и p16 INK4a может быть сигналом нарушения клеточного цикла и требует поиска факторов, определяющих одновременную экспрессию этих маркеров при данной патологии.
Introduction. Microsatellite instability is historically closely associated with the development of oncological processes. Early diagnosis of microsatellite instability as a marker for premalignancy, including in the case of endometrial hyperplasia (EH), which is recognized as a premalignancy lesion, is of interest. Identification of the mutational profile characteristic of malignant tumors in benign disease makes it possible to improve prognostic models and therapeutic tactics. Aim. Determination of clinical and anamnestic features of patients with EH and endometrioid adenocarcinoma in a comparative aspect, as well as structural features of microsatellite instability in the endometrium in patients with this pathology. Materials and methods. The study involved 120 women who were divided into 4 groups: group I – EH patients without atypia (n = 30); group II – patients with atypical EH (n = 30); group III – patients with endometrioid adenocarcinoma (n = 30); group IV – healthy women without somatic and gynecological pathology (n = 30). A comparative morphological study of endometrial samples was performed and levels of MLH-1, MSH-2, MSH-6 and PMS-2 expression were assessed. Results. It was revealed that most EH patients without atypia, patients with atypical EH, endometrioid adenocarcinoma complained of abnormal uterine bleeding; the history of patients of these groups is characterized by the presence of cardiovascular and endocrine diseases, and the gynecological history is characterized by the presence of uterine fibroids, benign breast diseases and pelvic inflammatory diseases. There was found a decrease in the MLH-1, PMS-2, MSH-2 and MSH-6 expression in endometrial biopsies of women with EH. Conclusion. Decreased expression of MLH-1, PMS-2, MSH-2 and MSH-6 in endometrial biopsies can probably be considered as a predictor of premalignant transformation, which requires further study in order to develop a program of malignancy risk assessment.
Introduction One of the criteria of impaired DNA repair is microsatellite instability (MSI) resulting from functional insufficiency of the mismatched nucleotide repair (MMR) system, a complex of proteins (MLH-1, PMS- 2, MSH-2, MSH-6). No data on the study of MSI in chronic endometritis (CE) were found in the available literature.The aim of the study was to determine the structural features of microsatellite instability in the endometrium in female patients with chronic inflammation of the uterine mucosa.Materials and methods Group I consisted of 30 women with morphologically confirmed high-grade CE; Group II consisted of 30 patients with low-grade CE; Group III consisted of 30 women who sought pregnancy planning and had histologically unchanged endometrium. The degree of CE in patients in groups I and II was variable. We analyzed the expression levels of MLH-1-, MSH- 2-, MSH-6-, and PMS-2-proteins in the endometrium by estimating the staining area of nuclei and cytoplasm of the affected cells over the entire slice area. Nonparametric statistical methods with Mann-Whitney test were used. The value of probability of error was set at 0.05.Results There was a statistically significant decrease in the level of MMR protein expression in the endometrial samples from the Group I patients compared to the same indices in the Group II and III women. No statistically significant results were found when analyzing the level of MMR protein expression depending on the severity degree of CE.Discussion There was a statistically significant decrease in the expression level of the markers studied (MLH-1, PMS-2, MSH-2, MSH-6) in endometrial specimens from patients with low-activity CE compared to uterine mucosa biopsy specimens from highly active CE and mid-stage endometrial secretion phase specimens. The described morphological features of the uterine mucosa in patients with low-activity CE are consistent with the findings of other authors. The literature provides indications of structural features of MSI in pre-tumor and tumor processes in the uterine mucosa.Conclusion Endometrial samples with low activity and various degrees of CE show statistically significantly lower expression levels of MLH-1, PMS-2, MSH-2, MSH-6 when compared to biopsy specimens from highly active CE and normal endometrial samples, which may indicate pathogenetic heterogeneity in the development of inflammation in the endometrium.
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