Иммуногистохимическое исследование пролиферативной активности опухолевых клеток при различных градациях аденокарциномы предстательной железы

Prostate cancer is one of the leading causes of men death in developed countries. Modern diagnostic methods, including a puncture biopsy of the prostate gland, make it possible to verify oncology in the early stages, however, routine studies do not always allow to predict the course of the disease and outcome. The aim of our study was to analyze the clinical, morphological and immunohistochemical features of the proliferative activity of adenocarcinoma cells using the Ki-67 marker, to compare the degree of proliferative activity in tumors of various degrees of malignancy (according to Gleason’s classification), as well as to compare this indicator with the clinical stage of the disease, the level of prostate-specific antigen in the blood, the size of the prostate gland. Materials and Methods: On the basis of the City Clinical Hospital No. 31 and the Veteran Hospital No. 2, paraffin blocks with material obtained as a result of prostate biopsy, transurethral resection, and radical prostatectomy were selected. A morphological and immunohistochemical study of the material with the Ki-67 marker and a quantitative assessment of the degree of proliferative activity were carried out. Data were analyzed using the STATISTICA 10.0 program using estimates of the normality of the data distribution according to the Shapiro-Wilk W-test, the significance of differences was estimated using the Mann-Whitney U-test, and correlation relationships using Spearman’s correlation coefficient. Results: Statistically significant differences in the degree of proliferative activity in groups differing in the degree of differentiation were revealed. A statistically significant direct correlation of moderate severity was revealed when comparing proliferative activity with the degree of differentiation according to the Gleason system (rs = 0.523) and the clinical stage of the disease (rs = 0.646). No statistically significant correlation was found between indicators such as prostate-specific antigen level, age, prostate volume, and proliferative activity index. Conclusion: taking into account the proliferative activity index in addition to clinical and morphological studies helps to diagnose and subsequently predict the course of prostate cancer.Актуальность. Рак предстательной железы является одной из ведущих причин смерти мужского населения от онкологических заболеваний в развитых странах. Современные методы диагностики, в том числе пункционная биопсия предстательной железы, позволяют верифицировать онкологию на ранних стадиях, однако рутинные исследования не всегда позволяют спрогнозировать течение и исход заболевания. Цель: провести анализ клинико-морфологических и иммуногистохимических особенностей клеток аденокарциномы, с использованием маркера Ki-67, сопоставление степени пролиферативной активности в опухолях различной степени злокачественности (по классификации Глисона), а также сравнение данного показателя с клинической стадией заболевания, уровнем простатспецифического антигена в крови, объемом предстательной железы. Материалы и методы: На базе ГБУЗ ДЗМ «Городская клиническая больница № 31» и «Госпиталь для ветеранов воин № 2» были отобраны парафиновые блоки с материалом, полученным в результате биопсии предстательной железы, трансуретральной резекции и радикальной простатэктомии. Проведено морфологическое и иммуногистохимическое исследование материала с маркером Ki-67. Полученные данные проанализированы при помощи программы STATISTICA 10.0 с использованием оценки нормальности распределения данных по W-критерию Шапиро-Уилка, достоверность различий оценивалась с помощью U-критерия Манна-Уитни, а корреляционные взаимоотношения с помощью коэффициента корреляции Спирмена. Результаты: Выявлены статистически значимые отличия пролиферативной активности в группах злокачественной опухоли с разной степенью дифференцировки. Статистически значимая прямая корреляция умеренной выраженности была выявлена при сопоставлении пролиферативной активности со степенью дифференцировки по системе Глисона (rs = 0,523) и клинической стадией заболевания (rs = 0,646). Между такими показателями, как уровень простатспецифического антигена, возраст, объем предстательной железы и индексом пролиферативной активности статистически значимых корреляционных зависимостей обнаружено не было. Заключение: учет индекса пролиферативной активности в дополнение к клинико-морфологическому исследованию способствует диагностике и последующему прогнозированию течения рака предстательной железы

Endometrial dysfunction caused by chronic endometritis: Clinical and morphological aspects

Objective: to determine the clinical and morphological aspects of endometrial dysfunction caused by chronic endometritis (CE). Subjects and methods. The study included 239 reproductive-aged patients: 93 were examined for abnormal uterine bleeding; 37 patients of them had a history of miscarriage and secondary infertility, 17 patients had primary infertility (Group 1). The remaining 105 patients with infertility were examined for future in vitro fertilization (Group 2). A comparison group consisted of 41 patients with normal menstrual cycles and reproductive function across the cycle, who had separate diagnostic curettage before forthcoming surgery for uterine myoma. All the women in Groups 1 and 2 underwent standard clinical and morphological investigations, histopathological examination of the material obtained during hysteroscopy with separate diagnostic curettage (Group 1), and aspiration biopsy (Group 2) with the sections being stained with hematoxylin and eosin and by Mallory's method. Immunohistochemical diagnosis was used to assess endometrial recep tivity to steroid hormones and glycodelin. Antibodies against CD4, CD8, and CD20 were employed to study local immunity. Results. In Group 1, 52 (55.9%) of the 93 patients admitted to hospital for abnormal uterine bleeding were found to have CE on the basis of a morphopathological examination of the material after separate diagnostic study. In Group 2, CE was established in 59 (56.9%) of the 105 patients after postmortem examination. The patients with CE had a history of reproductive significant infections, such as Chlamydia, Trichomonas, Ureaplasma Mycoplasma, cytomegalovirus, papillomavirus infections, genital herpes, genital candidiasis, and bacterial vaginosis. The CE groups showed functional disorders of the endometrial glandular and surface epithelium. In the middle stage of proliferation, the expression of glycodelin in the glandular epithelial cells was detected to be moderate to strong in 83.3%. During the periovulatory period, no secretion of glycodelin is of fundamental importance for the regulation of reproductive function because this protein has contraceptive activity, by blocking the binding of sperm to the zona pellucida. Accordingly, endometrial glycodelin production during the proliferative phase, which has been identified by the authors in patients with CE, may be one of the pathogenic mechanisms for the development of infertility. In addition, the patients in Groups 1 and 2 compared with those in the comparison group were noted to have a decrease in CD4 cell counts with a simultaneous increase in CD8 expression and a reduction in CD20 levels, especially in Group 2. Conclusion. The patients with SE were identified to have endometrial dysfunction characterized by lower reception to steroid hormones, impairment in glycodelin secretion, retardation in the development of pinopods and in the phase of the menstrual cycle, and local immunity disorders. The above endometrial changes should be taken into account in the pregravid preparation of patients with CE

Endometrial dysfunction caused by chronic endometritis: Clinical and morphological aspects

Objective: to determine the clinical and morphological aspects of endometrial dysfunction caused by chronic endometritis (CE). Subjects and methods. The study included 239 reproductive-aged patients: 93 were examined for abnormal uterine bleeding; 37 patients of them had a history of miscarriage and secondary infertility, 17 patients had primary infertility (Group 1). The remaining 105 patients with infertility were examined for future in vitro fertilization (Group 2). A comparison group consisted of 41 patients with normal menstrual cycles and reproductive function across the cycle, who had separate diagnostic curettage before forthcoming surgery for uterine myoma. All the women in Groups 1 and 2 underwent standard clinical and morphological investigations, histopathological examination of the material obtained during hysteroscopy with separate diagnostic curettage (Group 1), and aspiration biopsy (Group 2) with the sections being stained with hematoxylin and eosin and by Mallory's method. Immunohistochemical diagnosis was used to assess endometrial recep tivity to steroid hormones and glycodelin. Antibodies against CD4, CD8, and CD20 were employed to study local immunity. Results. In Group 1, 52 (55.9%) of the 93 patients admitted to hospital for abnormal uterine bleeding were found to have CE on the basis of a morphopathological examination of the material after separate diagnostic study. In Group 2, CE was established in 59 (56.9%) of the 105 patients after postmortem examination. The patients with CE had a history of reproductive significant infections, such as Chlamydia, Trichomonas, Ureaplasma Mycoplasma, cytomegalovirus, papillomavirus infections, genital herpes, genital candidiasis, and bacterial vaginosis. The CE groups showed functional disorders of the endometrial glandular and surface epithelium. In the middle stage of proliferation, the expression of glycodelin in the glandular epithelial cells was detected to be moderate to strong in 83.3%. During the periovulatory period, no secretion of glycodelin is of fundamental importance for the regulation of reproductive function because this protein has contraceptive activity, by blocking the binding of sperm to the zona pellucida. Accordingly, endometrial glycodelin production during the proliferative phase, which has been identified by the authors in patients with CE, may be one of the pathogenic mechanisms for the development of infertility. In addition, the patients in Groups 1 and 2 compared with those in the comparison group were noted to have a decrease in CD4 cell counts with a simultaneous increase in CD8 expression and a reduction in CD20 levels, especially in Group 2. Conclusion. The patients with SE were identified to have endometrial dysfunction characterized by lower reception to steroid hormones, impairment in glycodelin secretion, retardation in the development of pinopods and in the phase of the menstrual cycle, and local immunity disorders. The above endometrial changes should be taken into account in the pregravid preparation of patients with CE

Immunohistochemical study of Ki-67, p53 and Notch1 expressions in prostate cancer of different grades [Immunogistokhimicheskoe issledovanie ekspressii Ki-67, p53 i Notch1 v adenokartsinomakh predstatel'noi zhelezy razlichnoi stepeni zlokachestvennosti]

OBJECTIVE: To determine the prognostic value of the expression of Ki-67, p53, and Notch1 in the diagnosis of prostate cancer. MATERIAL AND METHODS: Surgical and diagnostic materials obtained from patients with benign prostatic hyperplasia, prostate intraepithelial neoplasia, and prostate cancer of different grades underwent studies; a total of 98 patients were examined. Cell antigens were determined using rabbit anti-Ki-67 monoclonal antibodies (Clone SP6), mouse anti-p53 monoclonal antibodies (Clone Y5), and recombinant anti-Notch1 antibodies (Clone EP1238Y). RESULTS: Comparing Ki-67, p53, and Notch1 expression indices revealed statistically significant differences. There was a significant direct correlation between Ki-67 and p53 expression indices and prostate cancer grade groups based on the morphological Gleason grading system (rs=0.736; p<0.001; rs=0.682; p=0.035, respectively) and a strong inverse correlation between Notch1 expression and prostate cancer grade groups (rs= -0.425, p<0.001). CONCLUSION: Notch1 expression in conjunction with the low proliferative activity of cells and the absence of p53 (Y5) protein may suggest that the mechanism of apoptosis is preserved in tumor cells, which expands indications for medical treatment of prostate cancer.ЦЕЛЬ ИССЛЕДОВАНИЯ: Определить прогностическую значимость экспрессии Ki-67, p53 и Notch1 в диагностике рака предстательной железы. МАТЕРИАЛ И МЕТОДЫ: Исследован операционный и диагностический материал, полученный от пациентов с доброкачественной гиперплазией, простатической интраэпителиальной неоплазией и раком предстательной железы различной степени злокачественности, всего 98 пациентов. Определение клеточных антигенов осуществлялось при помощи моноклональных кроличьих антител к белку Ki-67 (Clone SP6), мышиных антител к белку p53 (Clone Y5), рекомбинантных антител к белку Notch1 (Clone EP1238Y). РЕЗУЛЬТАТЫ: Выявлены статистически значимые различия при сравнении показателей экспрессии Ki-67, p53 и Notch1. Установлена достоверная прямая корреляционная связь между показателями экспрессии Ki-67, p53 и прогностическими группами рака предстательной железы, основанными на морфологической классификации по Глисону (rs=0,736, p<0,001; rs=0,682, p=0,035 соответственно), а также выявлена сильная обратная связь между экспрессией Notch1 и прогностическими группами рака предстательной железы (rs=–0,425, p<0,001). Заключение. Экспрессия Notch1 в сочетании с низкой пролиферативной активностью клеток и отсутствием белка p53 (Y5) может свидетельствовать о сохранности механизма апоптоза в опухолевых клетках, что расширяет показания к консервативному лечению рака предстательной железы

SOCIO-POLITICAL AND HISTORICAL TRANSFORM CONSTITUTIONALISM IN THE MODERN WORLD

The article explores different points of view regarding the dialectics of the socio-political and historical development of global constitutionalism and its relationship with changes in the socio-political and state-legal system on a planetary scale (as a historically integral part in the development of society at any stage of the historical era, opposite to autarkic tendencies; as a phenomenon inherent in modern society). In this regard, the paper concludes that the socio-political and historical transformations of global constitutionalism as a social concept in the near future will largely determine the main directions of the socio-political and state-legal development of nation-states. The purpose of the research: from the standpoint of the socio-philosophical methods of cognition of social reality and the ideas reflecting it, to analyze the socio-political and historical transformations of global constitutionalism in the modern world. Object of research: the phenomenon of globalization of socio-political, state-legal and financial-economic development of national societies and states as a phenomenon of social reality, highlighted in the social concept of global constitutionalism

Immunohistochemical expression of nanog protein in prostate cancer cells of distinct grade groups [ИММУНОГИСТОХИМИЧЕСКАЯ ЭКСПРЕССИЯ БЕЛКА NANOG В КЛЕТКАХ РАКА ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ РАЗЛИЧНЫХ ПРОГНОСТИЧЕСКИХ ГРУПП]

Prostate cancer is the most common type of cancer among men, which is mainly due to extensive use of screening tests and high total number of prostate biopsies. Verification of tumors with poorer prognosis is the primary goal of prostate cancer management. The study was aimed to determine the clinical and morphological associations and the prognostic value of the Nanog protein expression in prostate cancer of distinct Grade Groups. We used the prostate tissue specimens obtained during surgery, and the biopsy specimens, the total of 89 cases. Histological and immunohistochemical assessment was performed using antibodies to Ki-67 and Nanog. Correlations between the expression of markers and the Grade Groups were revealed using the Spearman's rank correlation coefficient, and the correlation with clinical and morphological characteristics was determined using the chi-squared test (χ2). There was a positive correlation between the expression of Ki-67 and Nanog, and the Grade Group numerical order (rs = 0.619, p &lt; 0.001 and rs = 0.786, p &lt; 0.001 respectively). We managed to find the relationship between the high Nanog expression and the extraprostatic extension (p = 0.041). High expression of Nanog protein in the prostate cancer cells was associated with a higher-grade adenocarcinoma and indicated a poor prognosis. © 2020 Pirogov Russian National Research Medical University. All rights reserved