Introduction. Human papillomavirus (HPV) infection with high-risk HPVs is an etiological factor in the development of cervical cancer, with HPV type 16 (HPV16) being the most common. The mechanisms leading to disruption of viral oncogene expression and initiation of epithelial cell transformation are poorly understood. Epigenetic regulatory factors, including cellular miRNAs, may play an important role in HPV-induced carcinogenesis, and aberrantly expressed miRNAs may be promising markers for the diagnosis of HPV-associated lesions.Aim. To search for miRNAs involved in the pathogenesis of HPV16-associated cervical cancer and to evaluate their diagnostic potential for the detection of cervical cancer and precancerous lesions.Materials and methods. MiRNA expression in clinical samples was assessed by both next generation sequencing and quantitative stem-loop polymerase chain reaction (sl-qPCR). Plasma miRNAs from patients with precancerous and cancerous lesions and healthy donors were analyzed using sl-qPCR. Loss of heterozygosity in cervical cancer samples was assessed by copy number ratio of MIR135A1 and ACTB genes. A total of 67 patients with cervical cancer, 21 with precancerous cervical lesions and 24 healthy donors were included in the study. The effect of DNA methylation on miRNA-135A1 expression was evaluated after treatment with a demethylating agent of the cervical HPV16-positive SiHa cell line. Changes in the expression of the HPV16 E6 oncogene were analyzed after transfection with synthetic analogues of the mature forms of miRNA-135А1 (miRNA-135a-3p and miRNA-135a-5p).Results. A significant decrease in the expression of miRNA-135A1 and miRNA-135A2 was detected in tumor tissue samples from HPV16-positive cervical cancer, which was confirmed by sl-qPCR in an independent panel of tumor samples. A decrease in miRNA-135A1 expression was shown to result from both loss of heterozygosity of the gene and aberrant DNA methylation. Transfection of mature forms of miRNA-135A1 into SiHa cells resulted in decreased expression of the E6 oncogene of HPV16. Blood plasma samples from patients with cervical cancer and precancerous lesions showed lower levels of miRNA-135a-3p than healthy donors, and ROC analysis indicated its high diagnostic potential.Conclusion. Levels of miRNA-135A1 are significantly reduced in cervical lesions, both in tumor tissue and plasma, and the ability of this miRNA to suppress the expression of the HPV16 E6 oncogene suggests its oncosuppressive properties. Thus, miRNA-135A1 can be used as a promising new marker for the diagnosis of HPV-associated lesions.

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).

ВведениеР ак яичников (РЯ) -одна из ведущих причин смертности от опухолей женской репродуктивной системы, занимает седьмое место в структуре смертности от всех онкологических заболеваний среди женщин.Прирост заболеваемости составляет 4,80% в год [1].Более чем в 70% случаев РЯ диагностируется Введение: прогноз пациенток с диссеминированным раком яичников после первичной неоптимальной циторедукции остается неблагоприятным.Оптимальные подходы к проведению лекарственной терапии у данной категории пациенток остаются неизвестными.Мы изучили эффективность дозоинтенсивной химиотерапии в данной категории больных

Введение: внутрибрюшинная (в/б) химиотерапия у больных раком яичников (РЯ) в 1 линии лечения показала позитивные результаты в трех рандомизированных исследованиях.Однако данный метод до сих пор не является рутинным в клинической практике.Материалы и методы: нами было проведено исследование 2 фазы по изучению 1 линии химиотерапии с в/б введениями, в которое включались больные РЯ с Ic -IV стадиями после первичной оптимальной циторедукции.Интраперитонеальные порт-системы устанавливались интраоперационно или лапароскопическим методом.Пациенты получали режим химиотерапии: паклитаксел 135 мг/м 2 в/в в 1-й день, цисплатин 75 мг/м 2 в/б во 2-й день и паклитаксел 60 мг/м 2 в/б в 8-й день, всего 6 курсов. А.С. Тюляндина, В

Background MOGCT is rare tumors and represent 2% of all tumors of the ovary. Fertility preserving surgery is the standard of care for pts with MOGCT. Comprehensive surgical staging involves unilateral adnexectomy, omentectomy, peritoneal biopsies, washings and lymph node sampling. Visual inspection has been suggested as an alternative. Proposed surgical approach includes complete resection of the tumor-containing ovary with sparing of fallopian tube, inspection and palpation of contralateral ovary, omentum, lymph nodes, and peritoneum, biopsy of any suspicious lesions or lymph nodes, and collection of peritoneal washing or ascites. The objective of the study was to describe the clinico-pathologic features and treatment outcome of all patients diagnosed with MOGCT at the largest Russian Research Cancer Center. Methods A total of 149 pts treated for MOGCT in our center between 1987-2018 were included into this retrospective study. All data including clinical symptoms, demographics, stage, surgery, chemotherapy, survival and fertility function were analyzed and assessed in univariate and multivariate analysis. The median age was 22 years (range, 12-49 years). 109 (73.2%) of 149 underwent fertility-sparing surgery followed by chemotherapy (ChT). Histologically 29.5% (n = 44) of cases were pure dysgerminoma. All pts received BEP/EP regimens as a first line treatment. 14 (9.4%) pts had gonadal dysgenesis. Results With median follow-up of 86 mo. (range 1-337 mo.) 5-year OS was 92%. The 5-year disease free survival (DFS) was 87% (9.4% pts relapsed). The 5-year DFS in pts with dysgerminoma and non-dysgerminoma was 98% and 91% respectively (p = 0,2). The 5-year OS in pts with stage I was 100% and stages II-IV was 91%. Complete response reached in 97 (67.3%) of 144 assessed pts, marker-negative partial response registered in 34 (23.6%) pts. After first-line ChT completion 34/144 (23.6%) pts underwent surgical resection of residual masses. Conclusions The BEP regimen is a standard of care and provides high cure rate. Fertility-sparing surgery is standart volume of surgery even in advanced stages of disease. The BEP regimen does NOT adversely affect on fertility function of pts. Legal entity responsible for the study The authors. Funding Has not received any funding. All authors have declared no conflicts of interest.

Aim: To perform a comparative analysis with simultaneous measurement of vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF1) and matrix metalloproteinase 7 (MMP7) in serum samples taken from healthy women and ovarian cancer patients; to perform association of these markers with their expression in primary tumors depending on clinical, morphological and biochemical characteristics of the disease and its prognosis. Materials and methods: We assessed 54 treatment-naïve patients with ovarian cancer aged from 23 to 74 years (mean ± SD, 53.2 ± 1.9), being at various FIGO stages of the disease. The control group consisted of 120 healthy women of matched age and reproductive status, in whom serum biomarker levels were studied. Patient survival was assessed by the Kaplan-Meier method, with survival curves compared with log-rank test. All analyses were done with “STATISTICA” and SPSS software. Results: Serum VEGF levels in ovarian cancer patients were significantly (p < 0.0001) higher compared those in the control. The most informative cut-off values differentiating the groups studied were serum VEGF values of < 350 pg/ml (median value in the control) and > 505 pg/ml (upper quartile in the control). With 505 pg/ml taken as a threshold, the test had sensitivity of 79.6% and specificity of 75%. Another cut-off value of serum VEGF level between the patients with ovarian cancer and the control group (510 pg/ml) was derived from ROC curves and 75% sensitivity and 78.2% specificity. No acceptable cut-off value for serum IGF1 to differentiate between the patients with ovarian cancer and the controls could be obtained from the ROC curves. Serum MMP7 levels in the patients with ovarian cancer were significantly higher than those in the control group (Mann-Whitney test p < 0.0001). With ROC curves, the best sensitivity to specificity ratio for MMP7 value of 4.6 ng/ml was obtained to differentiate between the patients with ovarian cancer and the controls (sensitivity 83.3%, and specificity 81%). The variance analysis did not reveal any association between serum VEGF, IGF1 and MMP7 and age of patients with ovarian cancer, tumor histology, concomitant somatic and gynecological diseases, and CA-125 levels. Serum VEGF and IGF1 levels did not correlate with the stage of ovarian cancer, in contrast to MMP7, whose levels were significantly higher in stages IIIc–IV. The median VEGF level significantly increased as the degree of differentiation decreased from 510 to 622 pg/ml (p < 0.002), while median IGF1, on the contrary, decreased from 219 to 116 pg/ml (p < 0.0001). There was a direct correlation between serum and tumor VEGF levels in ovarian cancer patients (r = 0.65, p < 0.0001). On the contrary, there was an inverse correlation between serum and tumor IGF1 levels (r = -0.68, p < 0.0001). Serum and tumor MMP7 levels remained unrelated to each other. Tumor VEGF, IGF1 and MMP7 content was unrelated to the age of the patients, their reproductive status, presence of concomitant somatic and gynecological diseases, histology of ovarian cancer, and serum CA-125 levels. VEGF levels in the tumor were not associated with the stage of ovarian cancer, but in patients with initial stages Ia and Ib stages MMP7 values significantly lower (2.1 ng/mg protein) compared to those in stages IIIc and IV (6.1 and 4.7 ng/mg protein, respectively, p < 0.05). Similar pattern was noted for IGF1: tumor IGF1 values in the patients with stages Ia–Ib were significantly lower (0.5 ng/mg protein) than those with stages IIIc–IV (median, 1.3–1.4 ng/mg protein). A significant increase in both serum and tumor VEGF levels was detected in the patients with ovarian cancer with decreased degree of differentiation. On the contrary, tumor IGF1 levels, but not serum ones, were significantly increased from 0.6 to 1.4 ng/ml in the patients with poorly differentiated ovarian cancer. MMP7 tumor expression did not depend on the degree of its differentiation. Serum VEGF levels above 700 pg/ml and tumor levels of above 590 ng/mg protein should be considered as unfavorable prognostic factors in patients with ovarian cancer.

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.

Leiomyomas predominate among benign nonepithelial tumors of the corpus uteri. Leiomyoma is commonly an asymptomatic tumor and detectable in most cases at routine gynecological examinations. However, some forms of leiomyomas have a definite metastatic potential and, despite its benign morphological signs, may metastasize to the lung. Fatal cases resulting from tumor spread along the postcava to the right atrium are described.

Background. The early diagnosis of ovarian cancer (OC) is an important problem in modern gynecological oncology due to significant detection rates for late-stage tumors. Intensive screening of patients from high-risk groups that include OC predisposition gene mutation carriers is indicated.Subjects and methods. An unselected group of 202 patients with OC and two control groups of blood donors: 591 healthy females; 1197 persons (including 591 females, 606 males) were examined. Patients and healthy individuals who identified themselves as ethnic Russians and residents of the Russian Federation participated in the study. Whole peripheral blood samples were collected at the Clinical Subdivisions of the N.N. Blokhin Russian Cancer Research Center and at the Department of Transfusiology of the Acad. B.V. Petrovsky Russian Research Center of Surgery in 2012–2013. Informed consent was obtained from all the participants. DNA was extracted using a Prep-GS-Genetics reagent kit. Real-time polymerase chain reaction genotyping assay was carried out by melting-curve analysis employing an BRCA SNP genotyping kit(BRCA1 and BRCA2 gene mutations) and original oligonucleotides (CHEK2, NBN, and BLM gene mutations). Thirteen population-specific mutations, including 7 (185delAG, 4153delA, 5382insC, 3819delGTAAA, 3875delGTCT, 300T>G, and 2080delA) in the BRCA1 gene, 1 (6174delT) in the BRCA2 gene, 3 (1100delC, IVS2+1G>A, and 470T>C) in the CHEK2 gene, 1 (657delACAAA) in the NBN gene, and 1 (1642C>T) in the BLM gene, were genotyped. Polymerase chain reaction was performed using a DTprime real-time detection thermal cycler.Results and discussion. BRCA1 and BRCA2 gene mutations were detected in 46 (22.8 %) patients with OC; the prevailing mutation in the BRCA1 gene was 5382insC (58.7 %). OC was diagnosed in 32.6 % of the patients aged 51 years or older. The rate of moderate-penetrance mutations (1100delC and IVS2+1G>A in the CHEK2 gene, 657del5 in the NBN gene, and 1642C>T in the BLM gene) was 0.5–1.0 % in the group of OC patients and 0–0.3 % in the control group of healthy women. The majority of these patients (5/6) were diagnosed with OC at age less than 50 years. The CHEK2 mutation, 470T>C, was more frequently encountered in the control group (6.6 %) than in the OC patient group (5.0 %). High rate of the CHEK2 mutation, IVS2+1G>A, was first shown for OC patients in the Russian Federation, the odds ratio was 11.9 (95 % confidence interval, 9.5–14.3; p = 0.056). It was preliminarily concluded that it played an important role in the development of OC in the Russian population; our findings should be verified in further investigations. The difference in the rate of mutations, such as 1100delC, IVS2+1G>A and 470T>C in the CHEK2 gene, 657del5 in the NBN gene, 1642C>T in the BLM gene, were insignificant in the patient and control groups, which may be related to the low population rate of these genetic markers and, in case of the CHEK2 mutation, 470T>C, may be linked to its low penetrance. By taking into account the fact that numerous studies have proven the clinical significance of all examined moderate-penetrance mutations whose prevalence in the Russian population has been confirmed by the authors of this paper, the inclusion of the mutations in a diagnostic panel to detect hereditary predisposition to OC is substantiated. The associated risks are higher for the rare mutations leading to the formation of truncated nonfunctional proteins, which are 1100delC and IVS2+1G>A in the CHEK2 gene, 657del5 in the NBN gene, and 1642C>T in the BLM gene. The penetrance of the CHEK2 mutation, 470T>C, is lower, which should be kept in mind during medical genetic counselling.Conclusion. The total rate of mutations in the BRCA1, BRCA2, CHEK2, NBN, and BLM genes in patients with OC was 30.7 %, which determines the expediency of molecular genetic screening in this category of patients.

The last decade is characterized by increased concern with problems of primary multiple neoplasm phenomena. Authors discuss vari- ous diagnostic methods used in the management of patients with multiple malignancies, in particular, in patients with colon cancer. Applicability of performing simultaneous gynecologic surgical procedures for colon cancer is evaluated.

Adenosquamous cell carcinoma of the cervix is a rare form of cancer of the cervix. Because of the small number of observations adenosquamous cell carcinoma of the cervix remains poorly understood disease, although the first mention of it dates back to 1956, when A. Glucksmann, and C.D. Cherry first described of mixed carcinoma (adenoacanthoma) of the uterine cervix.

The proteome of ascites and pleural fluids (AF and PF) was mapped in patients with ovarian cancer (OC). 240 and 190 proteins were identi- fied with a high degree of assurance in A F and PF, respectively . The major portion w as extracellular and membrane proteins, whi ch ac- counted for 45 and 49 % in AF and PF, respectively. Analysis of the proteomic maps of AF and PF indicated that 82 proteins were common to these biological fluids whereas 81 and 49 proteins were unique to A F and PF, respectively. A list of 46 potential markers for O C metastasis and potential markers for tropic OC metastasis over the peritoneal (17 proteins) and pleural (11 proteins) surfaces is given.

The prevention of cancer of the cervix uteri (CCU) is an interdisciplinary problem that may be solved only via joint efforts of gynecol- ogists, oncologists, virologists, and immunologists. Since there is currently strong evidence for the viral origin of CCU, vaccination is prominent in its primary. The present paper considers and comparatively analyzes 2 different lines of biotherapy for CCU.