EXPRESSION OF THE TUMOR-ASSOCIATED PROTEINS IN THE OVARIAN CANCER

With the help of monoclonal antibodies (MCA-1, MCA-3, G1 class immunoglobulins) and polyspecific antiserum (As) by means of immunoblotting (IB) the increase of the expression of the tumor-associated proteins (TAP) in the samples of the tumor tissues (in 94, 55 and 38% respectively), metastatic lymph nodes — LN(m+) and sera of the patients with ovarian cancer (OC) (in 82, 77 and ~100% of the cases, respectively), was detected. The important feature of As was the reactivity with the samples of the LN (m+) on the numerous proteins (>5-10) in 78% of the patients. The statistical analysis of the data using Student t-criterion revealed the significant differences (MCA-1, MCA-3) in the expression of the markers in the tumor tissues and blood sera of the oncological patients compar- ing with the samples of the adjacent tissues, blood sera of the patients with the other tumor localization and healthy donors (p<0,05). The further research using a larger amount of the clinical material and development of the more precise quantitative immunoenzyme analysis to measure TAP, is needed. It is possible that detection of TAP using MCA-1 and As may serve a basis for the creation of the test-system for the immunodiagnostics of the OC and determination of the stage of the tumor process

CLINICAL CHARACTERISTICS OF OVARIAN CLEAR CELL CANCER

The research has enrolled 96 patients with rare ovarian clear cell cancer treated at N.N. Blokhin Russian Cancer Research Center from 1978 to 2000. A necessity to divide patients into two groups has emerged after histopathological slide review. The first group included 71 patients with ovarian clear cell carcinoma (OCCC). Twenty five patients with mixed malignant epithelial ovarian tumor (MMEOT) with mandatory presence of clear cell component were included into the second group. Clinical par- ticularities of clear cell ovarian cancer were studied. We performed a comparative study of clinical course of OCCC and MMEOT. Our data suggest that clear cell ovarian cancer has a number of typical clinical and biological particularities both in OCCC and MMEOT

Multiple primary malignancies of female genital organs: ways of prevention

Prevention of cancer and its early diagnosis is today one of the promising lines of oncology. The identification of the hereditary forms of malignancies is particularly urgent, which prevents the development of tumor pathology in apparently healthy individuals the rela- tives of whom have cancers

Эпигенетические и генетические нарушения функций генов BRCA1 / 2 у больных солитарным раком яичников и раком яичников при полинеоплазии

Background. Ovarian cancer is a complex and poorly studied disease that kills nearly 70–80 % of patients. Therefore, practitioners are interested in any opportunity of improving survival of these patients. From this point of view, investigation of genetic and epigenetic functions associated with this pathology is quite promising.Objective: to assess clinical and morphological characteristics of tumors in ovarian cancer patients, considering the presence of mutations and methylation in the BRCA1/2 gene.Materials and methods. This study included 180 ovarian cancer patients (FIGO stage I–IV) treated in the N. N. Blokhin Russian Cancer Research Center between 2008 and 2019. Study participants were divided into 3 groups according to their BRCA status and the number of primary tumors. We collected and analyzed venous blood, biopsy samples of ovarian cancer, archived histological sections, and paraffin-embedded tissue blocks. DNA isolated from venous blood was used to identify the following germline mutation by pyrosequencing: BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, and BRCA26174delT. DNA isolated from biopsy specimens and paraffin-embedded tissue specimens was used to analyze methylation in the promoter regions of the BRCA1 and BRCA2 genes by bisulfite sequencing (PyroMark Q24 DNA Sequencer; Qiagen, USA) with specific primers targeting promoter regions of the BRCA1 and BRCA2 genes.Results. Molecular testing demonstrated that the frequency of BRCA1 gene mutations was 21.1 % (38/148) in patients with solitary ovarian cancer and 40.6 % (13/32) in patients with multiple primary ovarian cancers. The frequency of methylation of the BRCA1 gene promoter was 2.2 % (18/148) in patients with solitary ovarian cancer and 3.1 % (1 case) in patients with multiple primary ovarian cancers. All BRCA1 methylated ovarian tumors were serous adenocarcinomas, including high grade tumors in 15 patients (78.9 %) and low-grade tumors in 4 patients (21.1 %).Conclusion. Hypermethylation of the BRCA1 gene promoter was observed only in individuals with sporadic serous ovarian cancer. No methylation was detected in patients with non-serous ovarian cancer, as well as in patients carrying BRCA1 gene mutations (both with solitary ovarian cancer and with primary multiple ovarian tumors).Введение. Рак яичников (РЯ) – сложное и малоизученное заболевание, уносящее жизни до 70–80 % пациенток. Поэтому практических врачей интересует любая перспектива улучшения выживаемости данной категории больных. С этих позиций изучение генетических и эпигенетических функций, связанных с возникновением этой патологии, нам кажется своевременным и перспективным.Цель исследования – изучить клинико-морфологические особенности опухолей у больных РЯ с учетом наличия мутаций и метилирования генов BRCA1/2.Материалы и методы. В исследование было включено 180 больных РЯ (FIGO I–IV стадии), получавших лечение в ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России с 2008 по 2019 г. В соответствии с BRCA-статусом и количеством первичных опухолей пациентки были поделены на 3 группы. Объектами исследований явились венозная кровь больных, клинические образцы РЯ (биопсийный материал), а также архивные образцы гистологических препаратов и парафиновые блоки. Образцы ДНК из цельной крови пациенток протестированы на наличие герминальных мутаций BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, BRCA2 6174delT методом пиросеквенирования. ДНК из биопсийного материала и архивных парафиновых срезов проанализированы на наличие метилирования в промоторах генов BRCA1 и BRCA2 методом бисульфитного пиросеквенирования на приборе PyroMark Q24 (Qiagen, США) с использованием специфических праймеров, амплифицирующих локусы, содержащие промоторные области генов BRCA1 и BRCA2.Результаты. Проведенное молекулярно-генетическое тестирование показало, что частота встречаемости мутаций гена BRCA1 у больных солитарным РЯ составила 21,1 % (38/148), а у больных РЯ при полинеоплазии – 40,6 % (13/32). Частота встречаемости метилирования промотора гена BRCA1 у больных солитарным РЯ составила 12,2 % (18/148), а в группе больных РЯ при полинеоплазии – 3,1 % (1 наблюдение). В 100 % случаев опухоль яичников при наличии метилирования была представлена серозной аденокарциномой: в 15 (78,9 %) наблюдениях – high grade и в 4 (21,1 %) – low grade.Выводы. Гиперметилирование промотора BRCA1 было выявлено только в группе больных спорадическим серозным РЯ. Метилирование не было обнаружено у больных несерозным РЯ, а также у больных РЯ – носительниц мутаций гена BRCA1 (как при солитарном РЯ, так и при первично-множественном процессе)

Репродуктивная функция пациенток со злокачественными герминогенными опухолями яичников

Malignant ovarian germ cell tumors (MOGCT) generally affect young women. The optimal volume of surgical treatment is unilateral adnexectomy. BEP-regimen chemotherapy (ChT) is the most effective regimen of treatment. Since this disease affects mainly adolescents and young women of reproductive age, one of the most important priorities concerning this category of patients is the fertility preservation.The aim of this study was analysis of long-term effects of ChT on reproductive function in a large population of young women treated for MOGCT in our center.Materials and methods. Inclusion criteria in our study were MOGCT, fertility-sparing surgery, cisplatin- and etoposide-based induction ChT (BEP/EP regimen), age 16-49 years. Presence of menstruation before treatment; no relapse following ChT at least 1 year. Blood tests were taken for hormones of ovarian function (follicle-stimulating hormone, luteinizing hormone, estradiol, anti-Mullerian hormone (AMH), inhibin B) to assess their menstrual, reproductive function, post therapeutic status of pregnancy or delivery.Results. The median time from the end of ChT until the date of filling out the questionnaire was 90 months (12–228 months). 58 (93.5%) of the 62 patients received BEP/EP regimen as a first line treatment, 4 (6.5%) treated with other regimens. During the ChT 42 (71.2%) patients developed amenorrhea due to the toxic effect of ChT. Among 47 women with regular menstruation after completion of ChT 23/47 (49%) patients attempted conception, 18/23 (78.3%) women conceived, 20 live birth deliveries were received. Correspondingly there were 2/18 (11%) miscarriages and 6/18 (33.3%) terminations. Four women were pregnant at the moment of the analysis. Inhibin B level was normal in all 15 evaluated pts (median 74,4 pg/ml, range 10–120). Median of AMH level was 0,97 ng/ml (range 0.08-6). In 10 (52.6%) of 19 pts AMH level was < 1 ng/ml, that was considered a decrease of ovarian reserve. Злокачественные герминогенные опухоли яичников (ЗГОЯ) чаще встречаются у молодых женщин. Оптимальным объемом хирургического лечения в настоящее время признана односторонняя аднексэктомия. Химиотерапия (ХТ) по схеме ВЕР является наиболее эффективным режимом лекарственного лечения. Поскольку данным заболеванием страдают преимущественно девочки-подростки и молодые женщины репродуктивного возраста, одним из важнейших приоритетов у данной категории пациенток является сохранение детородной функции.Цель. Изучение овариальной и репродуктивной функции у больных ЗГОЯ после ранее проведенного комбинированного лечения, включавшего органосохранное лечение и ХТ.Материалы и методы. Критериями включения в настоящее рестроспективное исследование были: 1) морфологически верифицированная ЗГОЯ; 2) органосохраняющее хирургическое лечение (односторонняя аднексэктомия тубоовариэктомия); 3) проведение ХТ первой линии на основе цисплатина; 4) возраст 16–49 лет на момент начала ХТ; 5) наличие менструаций до начала лечения; 6) срок не менее 12 месяцев после завершения ХТ; 7) согласие пациентки. С целью оценки овариальной и репродуктивной функций яичников проведено исследование гормонального статуса: определение уровня фолликулостимулирующего гормона (ФСГ), лютеинизирующего гормона (ЛГ), эстрадиола, антимюллерова гормона (AMГ), ингибина Б.Результаты. Медиана времени с момента окончания ХТ до даты заполнения анкеты составила 90 мес. (12–228 мес.). 58 (93,5%) из 62 включенных в данный анализ пациенткам проведена современная схема ХТ (ВЕР/ЕР), 4 (6,5%) получили другие режимы. Во время проведения лекарственного лечения у 42 (71,2%) больных развилась аменорея вследствие токсического эффекта ХТ. Среди 47 женщин с регулярной менструацией после окончания ХТ 23 (49,0%) пытались забеременеть, беременность наступила у 18 женщин (78,3%). На этих 18 пациенток приходится 32 беременности, 20 (62,5%) из которых завершились срочными родами. Все рожденные дети здоровы и не имеют отклонений в развитии. Четыре (12,5%) женщины на момент заполнения анкеты были беременны. В 8 (25%) случаях беременность была прервана, в 6 из них – по желанию женщины. Уровень ингибина Б был нормальным у всех 15 пациенток, сдавших кровь (медиана 74,4 пг/мл, 10–120). Медиана уровня АМГ составила 0,97 нг/мл (0,08–6). У 10/19 (52,6%) пациенток уровень АМГ был менее 1 нг/мл, что отражает снижение овариального резерва

ARTIFICIAL MENOPAUSE AND EXPERIENCE OF CIMICIFUGA EXTRACT USE (KLIMADYNON)

Advances made in oncogynecology and improvements of surgical, radiation, and drug treatment provided relatively good sur- vival rates in patients with female genital organ lesions. However, this treatment often leads to postcastration syndrome mani- festations in most young women. New rehabilitation modalities for such female patients are important and urgent. It was inves- tigated whether Cimicifuga racemosa extract may be used for alleviation of postcastration syndrome symptoms and the results are encouraging

Early ovarian cancer: our view of the problem

The paper considers some pathogenetic aspects of ovarian tumor development, on the basis of which the authors recommend to perform more aggressive chemotherapy in patients with the so-called early stages of ovarian cancer

Clinical and histological criteria for sex cord ovarian stromal tumors

Aim: to identify clinical and histological criteria for sex cord ovarian stromal tumors (OSTs).Materials and Methods. The retrospective non-comparative study was based on the main inclusion such as histologically verified sex cord OSTs. A standard examination algorithm was analyzed (ultrasound, blood tests, CT or MRI of the abdominal and pelvic organs). All clinical data were obtained from patients treated and monitored in clinical units at the Blokhin National Medical Research Center of Oncology and the National Center of Oncology and Hematology of the Kyrgyz Republic.Results. Data were obtained on the frequency of necrobiotic changes, malignancy, disease stages and their impact on survival in 456 patients. The 10-year survival rate for OSTs patients with vs. without intra-tumor necrobiotic changes was significantly lower (17.2 % and 78.1 %, respectively).Conclusion. The main factors of unfavorable prognosis in patients with granulosa cell ovarian tumors were disease stage and intra-tumor necrobiotic changes

Clinical and histological features of purely stromal cell ovarian tumors

Aim: to identify clinical and histologic features of pure stromal ovarian tumors.Materials and methods. We analyzed the clinical data from patients treated and followed up at the Blokhin National Medical Research Center of Oncology and the National Center of Oncology and Hematology of the Kyrgyz Republic.Results. Data on necrobiotic changes, malignancy, stages of the disease and the survival of 14 patients with pure stromal ovarian tumors have been obtained.Conclusion. The main factors of unfavorable prognosis in patients with ovarian tecoma are tumor necrosis, degree of malignancy and mitotic activity

Quantification analysis of the expression of tumor-associated proteins in serum samples from patients with ovarian cancer and those with other tumor location. Possibilities of their use in the diagnosis and estimation of the extent of a tumorous process

The specific features of the expression of tumor-associated proteins (TAP) were immunologically studied in the sera of patients with ovarian cancer (OC) and other tumor location by means of immune sera (As) or monoclonal antibodies (MAb) to find out whether they could be used to diagnose and estimate the extent of a tumorous process.MAb 1 (to HEp-2 cell membrane proteins, larynx cancer), Ac4 (to a pool of two ovarian cystadenocarcinomas), and MAb 3 (to affinity-pu- rified proteins of the apparently intact human gastric mucosa) were used to examine the sera of patients with OC and other tumor location and positive responsiveness was detected in 82, ~100, and 77 % of cases, respectively. The differences in the expression of TAP in the patients versus healthy donors were shown to be statistically significant (p = 0.0001; p = 0.015; p = 0.01, respectively).The sensitivity of quantifying ELISA in detecting TAP was 78 and 85 % in patients with Stages I–II and III–IV OC, respectively; ~100 and 89 % in patients with breast cancer and in those with gastrointestinal tract cancer, respectively; and 60 and 14 % in patients with lymphopro- liferative diseases and healthy donors, respectively. Comparison of TAP detection rates in the authors’ test systems with multiplex testing with a biochip array of 12 tumor markers has shown that these test systems are at the world standard level