Background. The inclusion of lenvatinib in the immunotherapy regimen for patients with MSS/pMMR endometrial cancer (EC) is due to its ability to modulate the tumor microenvironment, which allows the use of pembrolizumab in low-immunogenic tumors. However, only 30 % of patients with advanced or metastatic EC have a clinical response when treated with pembrolizumab and lenvatinib. In this regard, there is an obvious need to identify biomarkers that allow accurate selection of candidates for this type of therapy.Aim. To determine the predictive value of subpopulations of lymphocytes and macrophages, their expression of PD-1, expression of estrogen receptors, as well as vessel density in immunotargeted therapy for advanced or metastatic EC.Materials and methods. An open-label non-randomized observational association study was performed, involving a total of 22 patients with advanced or metastatic MSS/pMMR EC treated with pembrolizumab and lenvatinib. Duration of clinical effectiveness was used as a parameter to stratify patients. Using TSA-associated multiplex immunofluorescence, the proportions of CD8+ T lymphocytes, CD20+ B lymphocytes, FoxP3+ T regulatory lymphocytes and CD163+macrophages in tumor samples before the start of immunotargeted therapy were analyzed.Results. Three microenvironmental parameters were found to be associated with duration of clinical efficacy: the proportion of CD20+ B cells, the proportion of FoxP3+ T regulatory lymphocytes, and the ratio of CD8+/CD20+ lymphocytes in the tumor microenvironment. However, the CD8+/CD20+ lymphocyte ratio had the greatest predictive value; a value below 3.219 was associated with long clinical efficacy in patients with advanced or metastatic EC.Conclusion. The ratio of cytotoxic and B-lymphocytes in the microenvironment is a reliable predictor marker of the duration of the period of clinical effectiveness of immunotargeting therapy in advanced or metastatic EC.
This paper presents an intelligent model based on the Pix2Pix conditional generative adversarial network that automates the process of predicting the recurrence of cervical malignancy in patients who have not yet undergone surgery. The implemented model accepts a pelvic MRI image as input data and provides an output probability of tumor recurrence and a generated image for the "post-operative" perspective. The presented model differs from its basic analogue by modifying the loss function for the problem conditions and replacing the standard generator with a convolutional neural network U-Net. Since the formulated problem belongs to the class of medical diagnostic tasks, the presence of false negatives of the intelligent model was reduced to zero by slightly increasing the number of false positives. In the process of comparative analysis of prognostic and real postoperative images, it was experimentally proven that the model not only accurately predicts the recurrence of the disease, but also generates almost identical centers of tumor foci and their relative areas on the magnetic resonance tomography image. The feasibility of modifying the basic version of Pix2Pix was confirmed by comparing the results of the two models using common quality metrics – precision, recall and their harmonic mean. The modification developed makes it possible to obtain prediction data in the shortest possible time, allowing it to be used in real-time mode.
Background. Determination of the feasibility of performing minimally invasive surgery for invasive cervical cancer and identification of criteria for optimal surgical access that ensures safety, effectiveness, and satisfactory immediate and long-term results remain challenging in gynecological oncology. The aim of the study was to evaluate the immediate and long-term treatment outcomes in patients with invasive cervical cancer who underwent radical hysterectomy via laparotomy compared to those who underwent minimally invasive surgery. Material and methods. Treatment outcomes of 91 patients with invasive carvical cancer were analyzed. The assessment of the objective tumor response to neoadjuvant chemotherapy using the RECIST scale (Response Evaluation Criteria in Solid Tumors) was confirmed by clinical, ultrasound and CT/ MRI findings. The Kaplan-Maier curves and the log-rank criterion were used to compare the time of relapse-free and overall survivals. Statistical analysis and visualization of the analysis results were performed using prism 9.5.1 (GraphPad, USA). Results. The presence of parametrial lymphovascular space invasion and the frequency of lymphadenopathy were comparable for both groups of patients. there were no statistically significant differences in the number of the resected lymph nodes, but there was a statistically significant difference in volume of blood loss and the duration of surgery between the groups (p=0.0001). Every third patient was diagnosed with stage IIIC after surgery (pelvic lymph node lesion). Intraoperative complications were significantly lower in the laparoscopy group than in the laparotomy group (6.7 % vs 13 %). No significant differences in the proportion of relapses of the disease between the groups were found (9.6 % in the laparotomy group vs 11.7 % in the laparoscopy group). There were no significant differences in overall and relapse-free survival between the groups. Conclusion. Minimally invasive surgery is a promising and adequate surgical technique for the treatment of cervical cancer. However, additional studies are needed to determine the indications for these surgeries.
Background. The age-standardized cervical cancer incidence rate in the Tomsk region in 2021 was consistently higher than the average for the Russian Federation (21.2 / 100,000 versus 13.6 / 100,000 women). Primary prevention of cervical cancer is best achieved by human papillomavirus (HPV) vaccination of girls. Aim. To evaluate HPV vaccine efficacy for the prevention of cervical cancer in the Tomsk region within the framework of implementation of two regional programs: “Prevention of gynecological cancer and rehabilitation of women diagnosed with gynecological cancer in 2008–2010” and “Urgent measures to improve cancer care for the population of the Tomsk region in 2011–2013”. Material and methods. We studied the tolerability and efficacy of HPV vaccination for the prevention of HPV-associated cervical cancer in 439 vaccinated girls aged 9–26 years during a follow-up time of 14-years. Results. The assessment of a 14-year follow-up study of the impact of HPV vaccination on HPV-associated cervical lesions has shown that HPV vaccine is safe and 100 % effective. Conclusion. Further prospects for primary prevention of cervical cancer before the introduction of vaccines against HPV infection in the national immunization schedule indicates the feasibility and real clinical effectiveness of the introduction of regional and regional programs with the development of a mathematical model for optimizing financial costs for primary prevention of cervical cancer, taking into account demographic parameters and socio-economic damage from cervical cancer in the study area.
Background . Ovarian cancer is the third most common cancer of the female reproductive system after cervical and uterine cancer and is diagnosed at stage III–IV in 2 out of 3 cases. Maintenance therapy with PARP inhibitors signifcantly prolongs disease-free and overall survival. The purpose of the study was to demonstrate long-term remission in a patient with advanced ovarian cancer using maintenance therapy with PARP inhibitors (olaparib). Description of the clinical case . A 54-year-old female patient with verifed stage IV ovarian cancer, peritoneal carcinomatosis and left-sided pleurisy received combined modality treatment, including 2 courses of neoadjuvant chemotherapy with paclitaxel/carboplatin, cytoreductive surgery and 6 courses of postoperative chemotherapy with docetaxel/cisplatin. The patient was diagnosed with a somatic BRCA2 gene mutation (c.3708delA), which was detected by tumor DNA sequencing. The patient received maintenance therapy with olaparib for 38 months, resulting in no evidence of disease progression. Conclusion . This clinical case demonstrates the feasibility of using maintenance therapy with PARP inhibitors in a patient with initially disseminated platinum-sensitive ovarian cancer. Olaparib maintenance therapy provides stable long-term remission with no signs of adverse events and determined effect on quality of life of the patient.
Background . Endometrial cancer (EC) is one of the most significant oncogynecological problems. The main mortality cause in this disease, as in the case of other malignant neoplasms, is the tumor progression. The presence of mutations associated with mismatch repair-deficient is of great prognostic importance. Immunotargeting therapy (ITT), lenvatinib in combination with pembrolizumab, seems to be the most effective solution in the second line treatment of advanced EC without microsatellite instability. At the same time, the group of such patients is heterogeneous in terms of progression-free survival (PFS) on ITT. So that it determines the continuing need to search for reliable parameters steadily associated with the PFS duration in this type of treatment. Aim . To analyze the clinical and morphological features in patients with advanced EC depending on the PFS duration on ITT. Materials and methods. The study included data on patients ( n = 36) with advanced EC who received ITT in oncological dispensaries in Siberia and the Russian Far East. The overall patients’ group was analyzed using the Kaplan-Meier method. PFS was defined as the time from the ITT initiation until progression or death against the background of treatment. The influence of the selected factors (clinical and morphological parameters, treatment features, and adverse events) on PFS was assessed using a log-rank criterion. The study participants were then divided into 2 subgroups (15 women and 9 women) according to median PFS. Mann–Whitney tests for independent samples (quantitative measures), and Fisher’s tests (qualitative measures) were used to identify significant differences in comparison subgroups for the selected factors. Differences were considered statistically significant when the significance level was reached ( p <0.05); data at the statistical trend level ( p <0.10) were also discussed. Results . In the study group, median PFS on ITT was 9.7 months (cut-off point), which was accepted as a response criterion. Among the 74 parameters reflecting clinical and morphological features in patients with advanced EC, metastatic lesions of pelvic lymph nodes ( p = 0.028), para-aortic lymph nodes ( p = 0.014), bone metastases ( p = 0.080), and degree of estrogen receptor expression in tumor cells ( p = 0.071) were associated with PFS. Partial regression as the maximal response to ITT (62.5 % vs 7.14 %, p = 0.011), as well as longer duration of response (median PFS 15.11 ± 1.10 months vs 4.47 ± 0.57 months, p = 0.00007), and the absence of foci in the pelvic/para-aortic lymph nodes (89 % vs 50 %, p = 0.069, and 89 % vs 47 %, p = 0.048, respectively), were more frequently observed in patients with a duration of median PFS ≥9.7 months compared to those with progression before 9.7 months. Stabilization as the maximum response to ITT (78.6 % vs 37.5 %, p = 0.072) was more frequently registered in the subgroup of patients with progression up to 9.7 months. Conclusion . ITT can be considered as a potentially promising therapeutic option in advanced EC. Further research in this direction should be aimed at finding criteria to identify patients with EC who would have most benefit from this type of therapy more accurately.
Deficient DNA mismatch repair (dMMR) is a rare molecular disorder found in 20-30 % of endometrial tumors. Laboratory identification of dMMR/microsatellite instability (MSI) has a high diagnostic value, since these impairments are considered as biomarkers of endometrial adenocarcinoma. They help to identify patients at high risk of Lynch syndrome, evaluate the disease prognosis, and estimate the efficacy of immune checkpoint inhibitors and their combinations. This review details current concepts of MSI diagnostics and discusses its predictive value in patients with endometrial cancer. It also describes a new diagnostic algorithm for the detection of dMMR and MSI.
Backgraound. High-grade serous ovarian carcinoma (HGSOC) is the most common type of ovarian cancer. The prevalence of BRCA1/2 germline mutations is the highest in HGSOC. patients with germline BRCA gene mutations are more likely to respond to platinum-based chemotherapy. Clinical trials demonstrate the effectiveness of PARP inhibitors in the treatment of BRCA-associated ovarian cancer. Re-administration of PARP inhibitors after response to platinum-based chemotherapy demonstrates an increase in progression-free survival rates regardless of BRCA status. it is important for understanding the development of molecular mechanisms of resistance to platinum drugs and PARP inhibitors, as well as for developing new treatment strategies and tools to overcome resistance. Case description. This clinical case of BRCA-associated hereditary ovarian cancer demonstrates the efficacy and good tolerability of PARP inhibitor maintenance therapy following the treatment of the first relapse, as well as the efficacy of re-administration of PARP inhibitors following the treatment of the second relapse. The short-course of re-treatment with PARP inhibitors was accompanied by the development of multidrug resistance. the overall survival time was 112 months. Conclusion. The presence of mutations in BRCA1/2 genes is a promising justification for the administration of maintenance therapy with PARP inhibitors. Re-administration of PARP inhibitor maintenance therapy for relapsed ovarian cancer is currently being considered as a possible therapeutic option. deciphering the molecular mechanisms of resistance to PARP inhibitors is of paramount importance for the development of new treatment strategies and tools to overcome chemoresistance, re-sensitization of the tumor to platinum-based drugs or PARP inhibitors.
Background. Endometrial cancer is the most common malignancy of the female reproductive system. Patients with metastatic endometrial cancer have the overall 5-year survival rate of less than 20 %. The efficacy of treatment of advanced endometrial cancer remains low; therefore, the search for novel approaches for treating endometrial cancer is of great importance.Case description. We report a case of a 68-year-old female who presented with advanced endometrial cancer with metastatic lesions found in the axillary and lumbar lymph nodes, liver and lungs. The disease progressed after third-line chemotherapy, with no deficiency in the DNA repair system. The patient was successfully treated with lenvatinib and pembrolisumab. The treatment was characterized by controlled minimal toxicity and a satisfactory quality of life. At 5 months, the patient is alive with stable disease.Conclusion. Despite the progress in treating endometrial cancer including chemotherapy and hormone therapy, the prognosis of patients with metastatic endometrial cancer is poor. The discovery of new molecular markers (MSI , PD -L1) made it possible to develop a clinical approach using a combination of pembrolizumab and lenvatinib for patients with no deficiency in the repair system, for whom, the standard chemotherapy is ineffective. The presented case gives hope for the treatment of this category of patients.
Background. Endometrial cancer is the most common malignancy of the female reproductive system. Patients with metastatic endometrial cancer have the overall 5-year survival rate of less than 20 %. The efficacy of treatment of advanced endometrial cancer remains low; therefore, the search for novel approaches for treating endometrial cancer is of great importance. Case description . We report a case of a 68-year-old female who presented with advanced endometrial cancer with metastatic lesions found in the axillary and lumbar lymph nodes, liver and lungs. The disease progressed after third-line chemotherapy, with no deficiency in the DNA repair system. The patient was successfully treated with lenvatinib and pembrolisumab. The treatment was characterized by controlled minimal toxicity and a satisfactory quality of life. At 5 months, the patient is alive with stable disease. Conclusion . Despite the progress in treating endometrial cancer including chemotherapy and hormone therapy, the prognosis of patients with metastatic endometrial cancer is poor. The discovery of new molecular markers (MSI , PD -L1) made it possible to develop a clinical approach using a combination of pembrolizumab and lenvatinib for patients with no deficiency in the repair system, for whom, the standard chemotherapy is ineffective. The presented case gives hope for the treatment of this category of patients.
The important role of human papillomavirus (HPV) of high carcinogenic risk in the emergence and development of cervical cancer is undeniable. Approximately 90 % of cases of verified cervical cancer are HPV positive. The level of infection with this virus exceeds that of gonococci, chlamydia and yeast infections. Currently, one of the most discussed issues is the possibility of the association of HPV with the risk of developing malignant neoplasms when localized in organs that are anatomically close to the cervix. One of these localizations is the body of the uterus. It is known that endometrial cancer is based on its pronounced hormone dependence. Nevertheless, many factors are involved in the carcinogenesis of endometrial neoplasms, including genetic and epigenetic disorders, as well as risk factors, which include alimentary, hormonal, hereditary causes. At the same time, a controversial issue is the involvement of HPV in the development of this type of cancer. The data on the presence of HPV in endometrial cancer are extremely contradictory: the researchers claim both the complete absence of the effect of the virus on the development of this type of cancer, and the detection of HPV in 60–80 % of cases of tumors. In this regard, it becomes necessary to systematize the currently available research results on this issue and to conduct a meta-analysis of the association of HPV infection with the risk of endometrial cancer.
The purpose of the study was to review available data on the combined use of local hyperthermia and chemotherapy/radiotherapy in the treatment of locally advanced cervical cancer, as well as to analyze longterm treatment outcomes.Material and methods. A systemic literature review was conducted using medline, cochrane library, and elibrary databases in the interval time between 2003 and 2020.Results. The review describes the mechanisms of biological efficiency of local hyperthermia and evaluates the effect of hyperthermia combined with chemotherapy and radiation therapy on cancer cells. Analysis of the thermobiological effects of local hyperthermia indicates that it is a potent sensitizer of cell killing by ionizing radiation and chemotherapy. The increase in tumor radiosensitivity is caused by the inhibition of the repair processes of damaged dna strands. Hyperthermia enhances perfusion and oxygenation of hypoxic tumor cells with a consecutive increase in tumor radiosensitivity. During chemotherapy, local hyperthermia ensures the maximum targeted delivery of cytotoxic agents to the tumor, thus increasing the effectiveness of treatment. Moreover, local hyperthermia has a direct cytotoxic effect on tumor cells. Randomized trials on the use of hyperthermia in the treatment of locally advanced cervical cancer have shown positive immediate and long-term treatment outcomes.Conclusion. Local hyperthermia combined with chemotherapy and radiation therapy is a promising treatment modality for locally advanced cervical cancer, because it can significantly improve treatment outcomes and reduce the frequency of early and late adverse effects. However, despite the available world experience, there are no unified methodological approaches to local hyperthermia, and therefore further research is required.
In 5 patients, a change in the genetic landscape from HPV16 positive high-grade squamous intraepithelial lesion (HSIL) to squamous cervical cancer was traced, which occurred in these patients within the period from 7 months to 5 years after diagnosing HSIL.MATERIALS AND METHODS:The DNA from paraffin blocks of dysplasia tissue and the tumor that emerged afterwards was used for the study, which was analyzed using the OncoScan FFPE microarray Assay Kit Affymetrix (USA) for genome-wide determination of gene abundance and 65 key somatic driver mutations of oncogenes and tumor suppressor genes.RESULTS:In the study of HSIL material, somatic mutations were observed in 4/5 cases, 18 different somatic driver mutations of the NRAS, EGFR, BRAF, KRAS, IDH2 oncogenes and TP53 suppressor genes were found and almost no CNA-Copy Number Aberration was identified. HSIL malignization is associated with the appearance of secondary driver mutations in oncogenes and tumor suppressor genes and a large number of structural and numerical CNA, the frequency of which correlates with the time of dysplasia malignization into cancer with a very high correlation coefficient r = 0.98, P = 0.004. The trees of dysplasia evolution into tumor were constructed for each patient.CONCLUSION:According to the results of the work, it is assumed that the initiation of the development of mucosa dysplastic changes is due to primary driver mutations. The formation of secondary driver mutations and CNA are genetic mechanisms of malignant transformation, while the scenarios of the evolution of dysplasia into a tumor are individual and very diverse.
Currently, studies highlighting features of emergence, development, clinical score and prognosis for patients with HPV-negative cervical cancer are scarce. However, the data regarding high recurrence rate and mortality in patients with HPV-negative head and neck cancer are demonstrated. Here, cervical canal and exocervical scraping samples collected from 116 patients with primary cervical cancer, I–IV stages, aged 24 to 79 years, were examined with real-time PCR assay for assessing prevalence of 12 high oncogenic risk human papillomavirus (HPV) strains, genotyping and viral load. It was found that 84 (72.4%) and 32 cervical cancer patients (27.6%) were positive and negative, respectively, for high oncogenic risk (HR) HPV strains. Based on these data, patients were further subdivided into two groups: HPV-positive and HPVnegative patient group. Genotyping HPV-positive samples revealed that HPV genotype 16 was found in 67.8% of cases that agrees with data published worldwide. In addition, relapse-free and overall survival (HPV-positive and HPV-negative patients) rate were also evaluated in both groups. It was demonstrated that survival rate was significantly decreased in HPVnegative cervical cancer patients additionally characterized by less favorable prognosis. Moreover, length of relapse-free survival as well as overall survival for HPV-positive vs. HPV-negative patients was 102 vs. 68 months as well as 52 vs. 83 months, respectively. On the other hand, it was demonstrated that recurrence rate, clinical score and progression of cervical cancer directly depend on cancer spread observed at primary medical examination. Of note, the majority of primary cervical cancer relapses are diagnosed within the first 2 years after completing treatment. In addition, an increasing relapse rate has been documented in cervical cancer patients at advanced stages. Upon that, biological cancer behavior remains poorly predictable even in patients at similar disease stage. Therefore, it is essential that HPV as an important prognostic factor would be taken into account for choosing proper therapeutic strategy for treatment of patients with cervical cancer.
The study included 168 patients with precancerous cervical lesions 37 with low-grade squamous intraepithelial lesions (LSIL), 131 with high-grade squamous intraepithelial lesions (HSIL), and 150 women, who had not abnormal cervical cell changes. All patients underwent full colposcopy assessment, cytological/histological examination, molecular detection and genotyping of high-risk human papillomavirus. Viral load and physical status of HPV-16 DNA was evaluated in cases of mono-infection (n=208). The prevalence of virus-positive cases among the patients with LSIL/NSIL and healthy women was 78.5 and 50.7 %, respectively. The frequency of recurrence in patients with LSIL and HSIL was found to be determined by the physical status of HPV-16. A significant difference in episomal, mixed and integrated forms of HPV-16 between patients with LSIL/HSIL and patients without abnormal cervical cell changes was found (p=0.0002).
Cervical cancer is the second most common cancer after breast cancer and the third most common cause of cancer-related death followed by breast and lung cancers among women worldwide. advances in diagnostic imaging techniques provide better assessment of regional and distant cervical cancer metastasis. the use of contrast-enhanced ultrasound is a revolutionary imaging modality; it has several advantages over ct: no radiation exposure, nephrotoxicity, obtaining real-time information, relatively low cost and ease of use. currently, the contrast agent sonoVue is widely used in ultrasound imaging of liver, kidneys and pancreas lesions, as well as for closed abdominal injuries, multiple organ failure, breast and prostate cancers, etc. However, the role of contrast-enhanced ultrasound in gynecology is not clearly established. one of the most effective tools for the detection of locally advanced cervical cancer is mRi, which is used mainly to determine the local extent of the tumor. However, the use of functional mRitechniques has not yet been included in the standards. cervical cancer tissue has been found to show significantly lower diffusion-weighted imaging (dWi) values than normal cervical tissue, thus facilitating the detection of tumor and its spread. dWiis also used for differentiating changes after biopsy from residual tumor and for identifying small lymph nodes. the pEt/cttechnique combines the metabolic images of pEtwith anatomical images of ctand is more accurate than high resolution ctalone, especially in determining the involvement of regional lymph nodes and distant organs. 18-Fdg-pEt/cthas been successfully used for accurate staging of the disease (especially late stage), assessment of treatment response, radiotherapy planning, and detection of disease progression. in patients with advanced stages of cervical cancer (iiBiV stage), the 18-Fdg-pEt/ ctfindings can determine the treatment strategy in most cases, primarily due to high sensitivity (75–100 %) and specificity (87–100 %) in the detection of lymph node metastases.
Visualization of sentinel lymph nodes (SLN) is now widely accepted for lymph node (LN) detection using a radioactive lymphotropic trace. Preoperative lymphoscintigraphy with intraoperative lymphatic mapping under gamma detecting probe guidance proved to be an easy and reliable method for SLN detection.Material and methods.In this article we present our experience in using laparoscopic gamma-probe for intraoperative visualization of sentinel lymph nodes in gynecological cancer.Results.Intraoperative visualization of sentinel lymph nodes in young cervical cancer patients and in patients with stage I endometrial cancer allowed us to perform radical surgery with personalization of the extent of lymph node dissection, especially for patients with low and intermediate risks of lymphogenic metastasis.
Visualization of sentinel lymph nodes (SLN) is now widely accepted for lymph node (LN) detection using a radioactive lymphotropic trace. Preoperative lymphoscintigraphy with intraoperative lymphatic mapping under gamma detecting probe guidance proved to be an easy and reliable method for SLN detection. Material and methods. In this article we present our experience in using laparoscopic gamma-probe for intraoperative visualization of sentinel lymph nodes in gynecological cancer. Results. Intraoperative visualization of sentinel lymph nodes in young cervical cancer patients and in patients with stage I endometrial cancer allowed us to perform radical surgery with personalization of the extent of lymph node dissection, especially for patients with low and intermediate risks of lymphogenic metastasis.
Проблема злокачественных опухолей женской репродуктивной системы продолжает оставаться актуальной в связи с отсутствием значимой динамики со стороны показателей эффективности лечения и выживаемости, а также четкой тенденцией омоложения данного контингента больных. В настоящей статье представлены основные задачи, решение которых оказывает влияние не только на эффективность проводимого противоопухолевого лечения, но и решает вопросы оптимизации объемов лечения, качества жизни и репродукции. Концепция сторожевых лимфатических узлов обретает особую ценность у категории больных, претендующих на органосохраняющее лечение при раке шейки матки. Применение нового отечественного РФП 99mТс-Al2O3 демонстрирует его эффективное накопление по сравнению с импортным аналогом, а его практическое применение позволяет облегчить интраоперационное выявление сторожевых лимфатических узлов. С целью прогнозирования течения местно-распространенного рака шейки матки возможно использование ряда тканевых маркеров: высокий уровень Ki-67 до неоадъювантной химиотерапии и гиперэкспрессия COX-2 и белка p16ink4a после проведения неоадъювантной химиотерапии коррелируют с неблагоприятным прогнозом. У больных с диссеминированным раком яичников определение индекса PIV и выполнение лапароскопии на первом этапе позволит объективизировать показания для проведения оптимальной и полной циторедукции. Не менее важным моментом является возможность прогнозирования эффективности химиотерапии у больных раком яичников. Детекция мутаций генов BRCA 1 и 2 лежит в основе персонализации лечения при раке яичников. В группе, представленной 178 больными раком яичников, выявлено 24 образца, гетерозиготных по мутациям BRCA 1,2 (13,6 %). Чаще всего присутствовали мутации BRCA1 5382insC (n=10, 42 %) и BRCA1 4153delA (n=8, 33 %).