1 ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России (Сеченовский университет), Москва, Россия; 2 ФНКЦ специализированной медицинской помощи и медицинских технологий ФМБА России, Москва, Россия Цель исследования -изучить механизмы роста лейомиомы матки большого размера (ЛМБР) на основании клинико-морфологического исследования с иммуногистохимической (ИГХ) характеристикой экспрессии ростовых факторов (TGFβ, PD-ECGF), маркеров стволовости (CD117/c-kit, Connexin 43, Nestin) и пролиферации (Ki-67). Материал и методы. Исследован операционный материал 38 женщин с простой лейомиомой матки (ЛМ), разделенных на две группы: 1-я (основная группа) -21 пациентка с ЛМБР (размер более 6 см в диаметре) и 2-я (группа сравнения) -17 пациенток с ЛМ малого размера (менее 4 см в диаметре). Каждую группу разделили на две возрастные подгруппы: пациентки в возрасте моложе 45 лет и старше 45 лет (подгруппы 1а (n=12), 1б (n=9), 2а (n=8) и 2б (n=9) соответственно). На гистологическом материале проведено ИГХ-исследование с антителами к TGFβ, PD-ECGF, CD117/c-kit, Connexin 43, Nestin и Ki-67. Результаты. Установлено, что механизмы роста ЛМБР простого гистологического строения связаны с увеличением количества зон роста в опухолях, усилением в них пролиферативной активности клеток, появлением клеток с признаками стволовости, что сочетается с сохранением последующего созревании опухолевых клеток и определяет доброкачественный характер ЛМБР. Заключение. Обнаружены отличия в молекулярном профиле ЛМБР и ЛМ малого размера, а также ЛМБР у женщин перименопаузального и молодого возраста по уровням экспрессии Ki-67, TGFβ, PD-ECGF, СD117 и Connexin 43, которые могут быть использованы для диагностики, прогнозирования и создания таргетных методов терапии. Ключевые слова: лейомиома матки большого размера, молекулярный профиль, механизмы роста.Objective -to investigate the growth mechanisms of large uterine leiomyoma (LULM) on the basis of a clinical morphology examination, by providing immunohistochemical (IHC) characteristics of the expression of growth factors (transforming growth factor-beta (TGFβ) and platelet-derived endothelial cell growth factor (PD-ECGF)) and markers of stemness (CD117/c-kit, Connexin 43, Nestin) and proliferation (Ki-67). Subject and methods. The investigators examined surgical specimens from 38 women diagnosed with simple uterine leiomyoma (ULM), who had been divided into two groups: 1) 21 patients with LULM (>6 cm in diameter) (a study group); 2) 17 patients with small ULM (<4 cm in diameter) (a comparison group). Each group was also divided into two age subgroups (younger (<45 years) and older (≥45 years) subgroups (1a (n=12), 1b (n=9), 2a (n=8) and 2b (n=9), respectively. Histological specimens were used to make IHC examination with antibodies against TGFβ, PD-ECGF, CD117/ckit, Connexin 43, Nestin, and Ki-67. Results. The growth mechanisms of LULM of simple histological structure were found to be associated with the larger number of growth zones in the tumors, with their enhanced cellular proliferative activity, and wit...
The endometrium may be the most convenient object of forecasting the development of the large uterine fibroid, as the object is available in the diagnosis of diseases of the uterus, changes in its cytokine profile linked with the growth of uterine fibroid. Immunohistochemically identification of high expression of Ki 67, TGF-, PD-ECGF in the endometrium allows to predict the development of large uterine fibroids.
We studied the expression and intracellular localization of ACA and TRA-1-81 in smooth muscle cell tumors. The study was performed on tissue specimens obtained during surgery from patients with uterine leiomyoma and leiomyosarcoma (mean age 34 and 51 years, respectively). ACA was present in leiomyoma, leiomyosarcoma, and control myometrium. Intracellular expression of ACA varied in different types of tumors and was minimum in normal myometrium and maximum in leiomyosarcoma. Membrane localization of the protein is typical of common and cellular leiomyoma, while in the growth zones of mitotically active leiomyoma and leiomyosarcoma the reaction product was primarily located in tumor cell cytoplasm. TRA was detected in some leiomyosarcoma cells. Thus, ACA dysregulation was revealed in the growth zones of leiomyomas and in leiomyosarcomas, which manifested in enhanced expression of this protein and its detachment from the plasma membrane, which leads ACA translocation into the cytoplasm and nucleus of tumor cells and potentiates their proliferative activity.
Tumors of the myometrium, reminiscent of leiomyoma with atypical location and aggressive growth, represent a diagnostic problem due to their common manifestations in various imaging techniques. These include various types of uterine leiomyomas, stromal endometrial tumors and rare tumors of cahal-like cells.
Vaginal biopsy specimens from premenopausal women with uterine lnyoma were studied by immunohistochemical methods using monoclonal antibodies to the differentiation antigens before and after hysterectomy. Immunocompetent cells (mainly CD8 + antigens) were detected in vaginal mucosa of controls and were virtually absent from specimens from the patients with uterine myoma. The content of immunocompetent cells in the vaginal mucosa did not change for at least 12 months after hysterectomy irrespective of the scope of intervention. Key Words: immunohistochem&try; vagina; local immunity; myoma; hysterectomyRecent immunological studies have revealed disorders in the immune system of patients with uterine myolna [8][9][10]. Suppression of T cells has been reported, but the data on the composition of T cell populations are contradictory [3][4][5].Systemic imlnunity has been extensively studied in patients with uterine myoma, while local imlnunity of the vagina was never researched. Cells capable of responding to antigens by immune reactions relatively independent of the systemic immune responses are present in the female reproductive system [2,6,13].Numerous plasma and T cells are present in the submucous layer of the uterus, vagina, and uterine tubes. The cervix uteri is the site of the highest immunological activity; the endometrium and Fallopian tubes contain few draining lymph vessels, and the local imlnunity of the vagina is still weaker [2]. The vagina is the inductive area of the mucosal imlnune response, and the antigen presentation is hormonally regulated [14].Research Center of Obstetrics, Gynecology, and Perinatology, Ru~ian Academy ef Medical Sciences; Institute of Human Morphology, Russian Academy of Medical Sciences, MoscowThe incidence of urogenital disorders increases after hysterectomy (HE) due to decreased ovarian function and impaired urogenital circulation 111]. These data suggest changes in the local immunity of the vagine after HE.To assess the role of local immunity of the vaginal mucosa in patients with uterine myoma in the development of urogenital and inflammatory processes in the vagina after HE is an impm~ant task. We compared local imnmnity of the vagina in prelnenopausal women with uterine myoma before and after HE. MATERIALS AND METHODSLocal vaginal immunity was studied in 39 women with uterine lnyolna of premenopausal age (43.9+ 5.3 years) with intact menstrual function before and 6 and 12 months after HE. Control group consisted of 10 healthy women aged 30-48 years.The most frequent diseases in the anamnesis were concomitant viral infections in childhood and cardiovascular and gastrointestinal diseases. Concomitant and previous gynecological diseases were salpingitis, underlying diseases of the cervix uteri, and exterual endometriosis. All patients were exa-
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