Endometrial hyperplasia as a risk factor of endometrial cancer

Endometrial hyperplasia (EH) is the precursor lesion for endometrioid adenocarcinoma of the endometrium (EC), which represents the most common malignancy of the female reproductive tract in industrialized countries. The most important risk factor for the development of EH is chronic exposure to unopposed estrogen. Histopathologically, EH can be classified into EH without atypia (benign EH) and atypical EH/endometrial intraepithelial neoplasia (EIN). Clinical management ranges from surveillance or progestin therapy through to hysterectomy, depending on the risk of progression to or concomitant EC and the patient´s desire to preserve fertility. Multiple studies support the efficacy of progestins in treating both benign and atypical EH. This review summarizes the evidence base regarding risk factors and management of EH. Additionally, we performed a systematic literature search of the databases PubMed and Cochrane Controlled Trials register for studies analyzing the efficacy of progestin treatment in women with EH.

Non-hormonal therapy of patients with fibrocystic mastopathy in combination with endometrial hyperplasia

Introduction. The article presents a comparative analysis of the treatment of patients with combined estrogen-dependent pathology of female reproductive system: fibrocystic mastopathy and endometrial hyperplasia without atypia. The experience of treatment with an indole-carbinol-containing drug as monotherapy while using a levonorgestrel-releasing intrauterine system is presented.Aim. To evaluate the clinical efficacy of indolecarbinol in the treatment of patients with combined estrogen-dependent pathology of the female reproductive system.Materials and methods. The authors studied the responses to the treatment of patients with fibrocystic mastopathy and simple endometrial hyperplasia (n = 65) with the indole-carbinol-containing drug at a dose of 400 mg once daily for 12 months. All patients were divided into two groups: Group I (n = 32) – women who refused hormone therapy (indole-carbinol monotherapy); Group II (n = 33) – the use of indole-carbinol while using the levonorgestrel-releasing intrauterine system. Diagnostic methods: clinical and laboratory examination, ultrasound examination of mammary glands and pelvic organs, mammography, nipple discharge cytology at baseline and 6 and 12 months after the start of therapy. Before study group assignment to treatment, all patients underwent hysteroscopy with endometrial biopsy and histological examination. Descriptive statistics were used to evaluate the data: p-values below 0.05 were considered statistically significant.Results and discussion. The presented experience in treating women with combined pathology of the female reproductive system (fibrocystic mastopathy and endometrial hyperplasia without atypia) with the indole-carbinol-containing drug showed high clinical efficacy in mastopathy (relief of mastodynia (83.0 ± 1.6%), improvement of the ultrasound view of BI-RADS (66.1 ± 1.4%), reductions in mammographic density (66.1 ± 2.1%, p < 0.05)), high tolerability and satisfactory compliance. This drug combined with hormone therapy is recommended for the treatment of endometrial hyperplasia.Сonclusion. The use of indole-carbinol in the treatment of benign hyperplastic processes in mammary glands and endometrial hyperplasia is pathogenetically substantiated and shows high clinical efficacy

The use of modern minimally invasive technologies and imaging (CT) methods in the diagnosis and surgical treatment of endometrial hyperplastic processes and combined gynecological pathology

On the basis of retrospective and prospective analysis of case reports of 540 patients with recurrent endometrial hyperplasia and combined intrauterine pathology (recurrent endometrial hyperplasia + hysteromyoma and/or adenomyosis) some aspects of surgical treatment of the pathology are considered, the effectiveness of different kinds of endoscopic operations is analyzed. Potentialities of spiral computerized tomography (SCT) for diagnosis of uterine disease are examined.

Pathogenetically oriented endoscopy in the treatment of endometrial hyperplastic processes

The experience of using electro destruction of the endometry in 60 patients showed that the method practically doesnt have any contraindications if applied for treating hyperplastic processes in endometry and helps to obtain stable therapeutic effect. It is reasonable to consider it particularly promising inpatients with relapsing endometrial hyperplasia resistant to hormonal therapy; in case of association with severe extragenital diseases electro destruction may appear an alternative both to hormonal therapy and surgical treatment.

PATHOGENETIC MECHANISMS OF BENIGN BREAST DISEASE DEVELOPMENT IN WOMEN OF FERTILE AGE WITH ENDOMETRIAL HYPERPLASIA

Proliferative changes in the mammary glands very often associate with gynecological diseases. It is the state of receptors for sex steroids in the tissue but not the absolute concentration of hormones in the blood that influences the development of breast and endometrial diseases. It is still unclear how the structure and properties of estrogen (ER) and progesterone (PR) receptors, associated with ESR1 and PRG gene polymorphisms, change. Thus, a new line of scientific research was the examination of microRNA role in the pathogenesis of benign breast diseases in women of fertile age with endometrial hyperplasia. It is known, that microRNAs are involved in many cellular processes, as they influence target genes. The aim of the study was to determine the prognostic significance of epigenetic markers in benign mammary dysplasia pathogenesis in women of fertile age with endometrial hyperplasia. Materials and Methods. The authors examined 69 women aged 18–49, 27 women with endometrial hyperplasia (EН) without atypia and 42 women with benign mammary dysplasia (BMD) with endometrial hyperplasia without atypia. We studied the expression levels of estrogen and progesterone receptors, and their isoform ratio in the blood serum. We also isolated miR-125b, miR-155, miR-222, and miR-429 by real-time PCR. Results. The prevalence of CC allele of the PvuII C/T polymorphism and GG allele of the Xbal A/G polymorphism in ESR1 gene estrogen receptor causes the BMD in women of fertile age with EH, leading to a decrease in ER sensitivity. Epigenetic changes at the microRNA level indicate a decrease in cell adaptiveness, an increase in their proliferative activity, and an induction of angiogenesis. High expression of miR-155, miR-222, and miR-429 indicates poor prognosis for breast cancer patients. The study of correlation of miR-155, miR-222, and miR-429 with the ESR1 estrogen receptor gene polymorphism showed, that the highest Pvull C/T (TT, TC, and CC) and Xbal A/G (AA, AG, and GG) scores were found in women of fertile age with BMD associated with EH. Conclusion. The results of the molecular genetic studies demonstrate the possibility to predict the occurrence and development of breast proliferative diseases in women of fertile age with endometrial hyperplasia. Key words: benign mammary dysplasia, endometrial hyperplasia, estrogen receptors, progesterone receptors, microRNA. Пролиферативные изменения в молочных железах очень часто возникают на фоне гинекологических заболеваний. Решающее значение в возникновении заболеваний молочных желез и эндометрия имеет не абсолютная концентрация гормонов в крови, а состояние рецепторов к половым стероидам в ткани. Остается открытым вопрос об изменении структуры и свойств эстрогеновых (ER) и прогестероновых (PR) рецепторов, связанных с наличием полиморфизмов кодирующих их генов (ESR1 и PRG). Новым направлением научного поиска стало изучение роли микроРНК в патогенезе доброкачественных заболеваний молочных желез при гиперплазии эндометрия в репродуктивном возрасте. Известно, что микроРНК участвуют во многих клеточных процессах, действуя на специфические гены-мишени. Цель исследования. Определить прогностическую значимость эпигенетических маркеров в патогенезе доброкачественной дисплазии молочных желез при гиперплазии эндометрия в репродуктивном возрасте. Материалы и методы. Было обследовано 69 женщин в возрасте 18–49 лет, из них 27 – с гиперплазией эндометрия (ГЭ) без атипии и 42 – с доброкачественной дисплазией молочных желез (ДДМЖ) при гиперплазии эндометрия без атипии. Исследовали уровни экспрессии эстрогеновых и прогестероновых рецепторов, соотношение их изоформ в сыворотке крови. Произвели выделение miR-125b, -155, - 222, -429 методом ПЦР в режиме real time. Результаты. В основе патогенеза развития ДДМЖ при ГЭ в репродуктивном возрасте лежит преобладание аллеля CC полиморфизма PvuII C/T и аллеля GG полиморфизма Xbal A/G гена ESR1 эстрогенового рецептора, что приводит к снижению чувствительности ER. Эпигенетические изменения на уровне микроРНК свидетельствуют о снижении адаптивных свойств клеток, увеличении их пролиферативной активности, индукции ангиогенеза. Высокая экспрессия miR-155, miR-222 и miR-429 является фактором плохого прогноза для больных раком молочной железы. При изучении взаимосвязи miR-155, -222 и -429 с полиморфизмом гена ESR1 эстрогенового рецептора, самые высокие показатели Pvull C/T (ТТ, ТС и СС) и Xbal A/G (АА, АG и GG) выявлены у женщин с ДДМЖ при ГЭ в репродуктивном возрасте. Выводы. На основании полученных результатов молекулярно-генетических исследований дано научное обоснование возможности прогнозирования возникновения и развития пролиферативных заболеваний молочных желез при гиперплазии эндометрия в репродуктивном возрасте. Ключевые слова: доброкачественная дисплазия молочных желез, гиперплазия эндометрия, эстрогеновые рецепторы, прогестероновые рецепторы, микроРНК.

Endometrial Metaplastic/Reactive Changes Coexistent with Endometrial Hyperplasia and Carcinoma: A Morphological and Immunohistochemical Study

The aim of this study was to assess the relationship between endometrial metaplastic/reactive changes (EMRCs) and endometrial neoplastic lesions. Twenty cases of “simple” (without architecture complexity) EMRCs coexistent with endometrial malignant/premalignant lesions, twenty cases of neoplasia-unassociated EMRCs, and eight cases of complex metaplastic lesions were assessed by immunohistochemistry. EMRCs coexisted with endometrioid carcinoma (n = 12), atypical endometrial hyperplasia (n = 3), serous carcinoma (n = 2), and clear cell carcinoma (n = 3). Neoplasia-associated EMRCs showed a mean Ki67 labeling index of 12.6% (range 0–30%); with nuclear atypia in 16/20 (80%) cases; diffuse p16 expression in 15/20 (75%) cases; and heterogeneous ER, PR, and vimentin expression. Compared to the associated neoplasia, EMRCs showed a lower Ki67 expression (p < 0.001) and higher p16 expression (p < 0.001). No EMRC case showed mitotic activity, PTEN loss, MMR deficiency, nuclear β-catenin, p53-mutant pattern, Napsin A, or AMACR expression. No significant differences were found between neoplasia-associated and neoplasia-unassociated EMRCs. Complex metaplastic lesions showed a lower Ki67 expression than EMRCs (p = 0.044) and PTEN loss in 5/8 cases, even in the absence of nuclear atypia. In conclusion, neoplasia-associated simple EMRCs may show evident atypia and a worrisome immunophenotype, but no data support their involvement in endometrial carcinogenesis. Architectural complexity appears as a crucial factor to identify precancerous lesions.

Effichiency of contemporary methods of internal endometriosis (adenomyosis) treatment

The main treatment method of the internal endometriosis nowadays is still surgical method - hysterectomy by laparoscopic or laparotomic way. The histeroscopic endometrial resection (ablation) is an alternative with regard of hysterectomy in female patients with surface adenomyosis forms in absence of pain syndrome. According to available information on our investigation, the endometrial resection (ablation) is very effective in 72% of female patients with adenomyosis combined with recidive endometrial hyperplasia.