Objective of the study — is to analyze the association between the level of methylation of miRNA genes in the tumor with concentrations of VEGF in the blood plasma of patients with ovarian cancer and to evaluate their potential for the prognosis of overall survival.
Materials and Methods. 26 primary patients, previously untreated, with serous ovarian cancer at various stages of the tumor process were examined in accordance with the TNM classifi cation of WHO (2014). The present work reports the levels of methylation of 14 miRNA genes (MIR124–2, MIR124–3, MIR125B-1, MIR127, MIR129–2, MIR132, MIR137, MIR203A, MIR34B, MIR34C, MIR375, MIR9–1, MIR9–3, MIR339) identifi ed in 26 primary tumors and 19 peritoneal metastases of patients with ovarian cancer, compares these levels with the content of VEGF in the blood plasma of these patients and underlines their role in the assessment of the prognosis of the disease.
Results. It was revealed, that there is a direct correlation between VEGF concentrations in the blood plasma of patients with ovarian cancer with the levels of methylation of 5 miRNA genes in the tumors (MIR124–2, MIR125B-1, MIR127, MIR129–2, MIR9–3) and 3 miRNA genes in metastases (MIR124–2, MIR124–3, MIR203A). Analysis of variance confi rmed that with an increase in VEGF concentrations in the blood plasma, a statistically signifi cant increase in the level of methylation of 2 miRNA genes in the tumor tissue was revealed: MIR124–2 and MIR127, and the strong tendency to a difference in the median methylation of MIR129–2 and MIR9–3 genes was found, whereby the difference in the level of methylation of MIR9–3 gene was observed only in the median of VEGF. Synchronicity in the changes of the VEGF content in blood plasma and the level of methylation of the following 4 miRNA genes- MIR124–2, MIR129–2, MIR9–2, MIR-339 in tumor was observed. The highest overall survival rates were found in ovarian cancer patients who had simultaneously low levels of VEGF in blood plasma and the level of methylation in the tumor of a group of 3 miRNA genes: MIR124–2, MIR125B-1, MIR375. Combinations of VEGF parameters in blood plasma with the level of methylation of the other miRNA genes that have been studied, didn’t disclose any relationship with long-term results of the treatment. A multivariate analysis (Proportional hazard (Cox) regression) of the relationship between overall survival and VEGF concentrations in blood plasma and the level of methylation in the tumor of miRNA genes (MIR124–2, MIR125B-1, MIR129–2, MIR375) showed that the latter affect the long-term outcomes of the treatment of ovarian cancer patients to a greater extent than VEGF does.
Conclusion. The joint determination of VEGF concentrations in blood plasma with levels of methylation of miRNA genes in the tumor (MIR124–2, MIR125B-1, MIR129–2, MIR375) permits to enhance our understanding of ovarian cancer pathogenesis and to make more precise prognosis of the disease in ovarian cancer patients, which indicates the need for further research.
Keywords: ovarian cancer, VEGF, miRNA, methylation
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Objective of the study — is to compare the cosmetic outcome after surgical intervention in patients with breast cancer who had radiopaque “marker” placed in the primary tumor site, with patients in whom the tumor was not marked.
Materials and Methods. The study comprised 162 patients from 30 to 60 years of age, diagnosed with breast cancer of any molecular subtype, T1–3, N any M0 stage, who received neoadjuvant drug therapy at the fi rst phase of the treatment. 83 patients underwent radiopaque “marker” placement into the center of the tumor bed before and during neoadjuvant drug therapy, in 79 patients the tumors were not marked. To assess the well-being of the patients, the Russian-language questionnaire BREAST-Q, developed by Pusic et al. at Memorial Sloan-Kettering Cancer University of British Columbia in 2009 was used.
Results. The study primarily evaluated the effect of neoadjuvant therapy in the compared groups, and found no statistically signifi cant differences in respect to complete (29,8 %/39,5 %), p = 0,135 and partial (70,1 %/60,5 %) clinical responses, p=0,324. Thereby, the rate of organ-preserving surgeries was higher in the group of patients who had had their tumors marked, compared to the second group and made up 92,5 % versus 47,1 %, p < 0,001. Both the volume of the tissue excised during the organ-preserving surgery and the length of the skin incision were signifi cantly smaller in patients whose primary tumor had been marked. The average volume of the sector removed in patients who had no tumor marking and underwent organ-preserving surgeries made up 12,15 cm3 ± 0,373, in patients whose tumor had been marked — 3,27 cm3 ± 0,136, p < 0,001. The length of the skin incision in patients who underwent organ-preserving surgery and didn’t have marker placement was 6,5 cm ± 0,348, and in patients with marker — 4,98 cm ± 0,175, p < 0,001. The study also focused on the rate of “positive” margins after immediate intraoperative examination. This indicator was higher in the group without primary tumor marking and was 7,59 %, without marker – 4,8 %. The differences in the necessity for reresection in the groups are close to significance level, p = 0,069.
The thorough analysis of the questionnaire data yielded satisfactory results, characterized by an improvement in physical (the difference is signifi cant with p < 0,001), psychosocial (the difference is signifi cant with p < 0,001) and sexual (the difference is signifi cant with p < 0,001) well-being, satisfaction with the appearance of the breasts (the difference is significant with p < 0,001) of women who underwent “marker” placement in primary tumor during neoadjuvant drug treatment.
Conclusion. Focusing on the obtained statistical results, it can be concluded that marking of the primary tumor before neoadjuvant drug therapy allows to perform more aesthetically appealing and pleasing operations in full compliance with radicality.
Keywords: breast cancer, tumor marking, radiopaque marker
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Objective of the study is to summarize the available data on the intricacies of etiology and diagnosis, clinical picture and various approaches in the treatment of cerebral metastases of ovarian cancer.
Materials and Methods. The review comprises the analysis of the articles presented in PubMed database, publications for the period from 1966 to 2020 were studied.
Results. The review of the literature on the subject gives ground to assert that the brain is rarely susceptible to metastases in patients with malignant ovarian neoplasms. This problem is extremely poorly studied due to its rarity, but it still occurs in modern oncology.
Conclusion. The key clinical problem relates to the rare incidence of ovarian cancer metastases to the central nervous system (CNS). Multidisciplinary approach is used for the selection of treatment strategy. This issue requires further research.
Keywords: ovarian cancer, metastases to central nervous system (CNS), radiation therapy, antitumor drug treatment, surgical treatment
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Introduction. Cervical cancer is the fourth most commonly occurring cancer in women globally. Treatment standards of early stage cervical cancer include radical hysterectomy and/or radiation therapy (RT), while for locally advanced cancers, radiation therapy, sometimes in combination with chemotherapy are the standard-of-care treatment. Complete clinical response after radiation therapy is achieved only in a fraction of patients, which is due to the development of tumor cell radioresistance. Thus far, a considerable number of markers for the prediction of response to radiation therapy has been identifi ed, however, none of them has entered clinical practice yet.
Objective of the study — is bioinformatics and laboratory screening of molecular markers for minimally invasive testing of cervical cancer sensitivity to radiation therapy.
Materials and Methods. The study was conducted on 300 patients with cervical cancer (IB1, IB2, IIA1, tumor < 4 cm) and 30 donors who had no oncologic disease. The Cancer Genome Atlas database was analyzed to identify potential markers, and the TCGABiolinks R language package was used to obtain the data. The GISTIC algorithm was used to identify regions of the genome, whose size changed signifi cantly in a number of tumor samples. To validate the data of bioinformatics analysis, tissue sections from FFPE-blocks and blood plasma of patients were used. The markers detected at the bioinformatics stage were validated using Real-Time-PCR in DNA samples isolated from tumor and normal cells, as well as in extracellular DNA samples. Tumor and normal cells were isolated from cervical tissue using non-contact laser capture microdissection. Linear accelerator Varian TrueBeam was used to deliver external beam radiation therapy in VMAT/IMRT mode (total focal dose of 50 Gy). Mann-Whitney U test with Bonferroni correction was used to assess the differences in gene copy- number.
Results. Analysis of the results of radiation therapy allowed to divide patients into 2 groups — sensitive to radiation therapy (n = 170, group 1) and resistant (n = 130, group 2). A number of genes associated with copy- number change and sensitivity to radiation therapy were identifi ed at the stage of bioinformatics analysis — ERBB2, BIRC2, TRPC6, YAP1, MIR569, LRRC31, SPRED3, MIR4456, CYP-1A, A2, CYP11A1, MIR4786, TIGD1, GPX4, ST14, LINC00167, LINC00558, LINC00400, FOXO1, ENOX1, EPSTI1, NEK5, KCTD4, SERP2, MIR621, PTEN, SOD2, MIR3939, ATM, CASP-1, -4, -5, CHEK1, and H2AFX. Copy-number variants of these genes were analyzed in the DNA of tumor and normal cells of cervical tissues. Patients in group 1 exhibited a decrease (p < 0.05) in H2AFX, ATM, CHEK1, LINC00400 gene copy-number and an increase (p < 0.05) in CASP-1, -4, -5, CYP1-A1, -A2, and GPX4 gene copy-number in tumor cells, as compared to those copy-number variants in normal cells. A decrease (p < 0.05) in CASP-4, -5, CYP1A1, YAP1 gene copy-number and an increase (p < 0.05) in H2AFX, CHEK1, ERBB2 and BIRC2 gene copy-number in tumor cells, as compared to those variants in normal cells were observed in group 2 patients. The difference between H2AFX, CHEK1, ERBB2, LINC00400, CASP-4, -5, and CYP1A1 gene copy-number variants in tumor cells of two groups of the patients with cervical cancer was statistically signifi cant (p < 0.05). H2AFX, CHEK1, LINC00400, CASP-1, -4, -5, CYP1-A1, -A2, GPX4, YAP1, ERBB2 and BIRC2 genetic loci copy-number was further analyzed in cfDNA. A decrease (p < 0.05) in H2AFX, CHEK1, LINC00400 gene copy-number and an increase (p < 0.05) in CASP-4, -5, CYP1-A1, -A2 and GPX4 gene copy-number were found in group 1. Group 2 exhibited a decrease (p < 0.05) in CASP-4, -5, CYP1-A1 and YAP1 gene copy-number and an increase (p < 0.05) in H2AFX, CHEK1, ERBB2 and BIRC2 gene copy-number variants, as compared to those copy-number variants in donors who had no oncologic disease. The difference between H2AFX, CHEK1, ERBB2, BIRC2, LINC00400, CASP-4, -5, and CYP1A1 gene copy-number variants in tumor cells of two groups of patients with cervical cancer was statistically signifi cant (p < 0.05).
Conclusion. Markers, identifi ed by a combination of bioinformatics and molecular genetic approaches — which are indicators of H2AFX, CHEK1, ERBB2, BIRC2, LINC00400, CASP4, CASP5 and CYP1A1 copy-number variation in cfDNA — can become a basis of minimally-invasive determination of cervical cancer sensitivity to radiation therapy.
Keywords: cervical cancer, gene copy-number, radiation therapy, cell-free DNA
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The article presents the result of surgical treatment of a patient with stage III vulvar cancer (with metastasis to the inguinal lymph node). The choice of the optimal treatment for this patient population is a challenging issue in oncology due to frequent complications both occurring in the primary tumor site, the zone of inguinal and femoral lymphadenectomy, and associated with the exacerbation of concomitant extragenital diseases. This case highlights the need for early diagnosis and treatment of precancerous conditions of the female external genital organs due to the high probability of their transformation into malignant neoplasm. Surgical treatment of vulvar cancer is the main method which allows to achieve long-term remission.
Keywords: vulvar cancer, surgical treatment, squamous cell invasive cancer, Paget’s disease
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Lymphedema of the lower extremities is one of the most severe complications after radical hysterectomy with pelvic lymphadenectomy in patients with cervical cancer. This condition occurs when, as a result surgery, the lymphatic system cannot maintain the homeostasis of tissue fl uid, which leads to the accumulation of the latter in the intercellular spaces and, consequently, to the swelling of the legs. In this case, patients experience a feeling of heaviness, tension, functional limitations in the lower extremities, which can cause psychological stress and affect their quality of life. The incidence of lower extremity lymphedema after radical surgery for cervical cancer varies from 1,2 % to 47,6 %, and while there are programs specially designed for the prevention of upper extremity lymphedema in breast cancer patients, lymphedema of the lower extremities remains insuffi ciently studied. Therefore, it seemed appropriate to us to consider this problem based on a specifi c clinical case.
Keywords: lymphedema of the lower extremities, prevention, cervical cancer, radiation therapy, radical hysterectomy
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