Objective of the study — is to conduct a systematic analysis of the data available in current literature on the role of both mutations in gene BRCA1, the change of protein BRCA1 function in the process of carcinogenesis and in the effectiveness of chemotherapy.
Materials and Methods. The review comprises the data from foreign and Russian articles found in Pubmed on the subject which have been published over the past 10 years.
Results. BRCA1 participates in the processes of repair of DNA damages assisted by administration of traditional anticancer agents, including platinum preparations, and controls the manifestation of their antitumor activity. Concurrently, the functioning of BRCA1 depends on its interaction with numerous cellular proteins, and the level of BRCA1 is supported in the result of epigenetic regulation of BRCA1 gene expression. The present review considers major epigenetic mechanisms of the regulation of gene BRCA1 expression, which include DNA methylation, histone covalent modifi cations, regulation by transcription factors, as well as cell signaling pathways, which participate in these processes.
Conclusion. BRCA1 plays an important role in DNA repair both by homologous recombination and by non-homologous DNA end-joining, thus ensuring the maintaining of genome stability. Impairment of BRCA1 protein function, caused by mutation in its gene, is associated with the development of breast cancer, ovarian cancer and some other forms of malignant neoplasms. It is necessary to conduct further research in this area.
Keywords: BRCA1, DNA repair, epigenetic regulation, DNA methylation, histone modifi cation, transcription factors, cell signalling pathways.
 Full text (in Russian)

Objective of the study is to conduct a systematic analysis of the literature data on the novel molecular biology research as well as on the modern trends in diagnosis and prevention of malignant tumors induced by human papillomavirus (HPV). Particular emphasis is being put on a potential role of human papillomavirus in the development of tumors of various anatomical localizations.
Materials and Methods. The review includes the data from foreign and Russian articles having been published in PubMed database on the subject over the past 15 years.
Results. Extensive epidemiological and molecular biological studies demonstrated the etiological role of human papillomaviruses of high carcinogenic risk in the development of cervical cancer as well as of other tumors of anogenital tract and oropharynx. The potential role of human papillomaviruses in the development of tumors of other anatomical localizations is not suffi ciently explored and requires further research in this respect. The analysis of molecular mechanisms of virusinduced carcinogenesis allowed to devise new approaches to diagnosis as well as to preventive vaccination against tumors caused by human papillomavirus.
Conclusion. The identifi cation of molecular mechanisms of HPV-induced carcinogenesis provides a basis for the development of novel diagnostic and therapeutic approaches to the treatment of HPV-associated lesions of various anatomical localizations.
Keywords: human papillomavirus (HPV), high-risk human papillomavirus (high-risk HPV, HR-HPV), HPV-associated human tumors, cervical cancer.
 Full text (in Russian)

Objective of the study is to analyze the data of international investigations available in the literature on the special aspects of recognizing menstrual cycle in women with hormone receptor — positive breast cancer after chemotherapy when making the choice of ovarian suppression and adjuvant treatment.
Materials and Methods. The review includes the data of foreign and Russian articles found in PubMed on the subject which have been published over the past 15 years.
Results. The article introduces a possibility of the use of predictors of menopause induced by cytostatic treatment, that can be relevant in taking a decision regarding a prescription of adjuvant ovarian suppression.
Conclusion. It is necessary to conduct a large-scale research with the purpose to obtain more accurate techniques of the assessment of ovarian function after chemotherapy in women in pre-menopause and their implementation into clinical guidelines on adjuvant treatment of early breast cancer.
Keywords: breast cancer, pre-menopause, ovarian suppression.
 Full text (in Russian)

Objective of the study is to determine the nature (multiple primary or metastatic) of the origin of synchronous endometrioid malignant tumors of uterine corpus and the ovaries., as well as to clarify the role of endometriosis in endometrioid ovarian cancer carcinogenesis.
Materials and Methods. Clinical and morphological characteristics of patients with synchronous endometrioid multiple primary malignant ovarian tumors and tumors of uterine corpus (n = 66) and patients with endometrioid adenocarcinoma of uterine corpus and the ovaries (n = 60) has been analyzed. Molecular genetic technologies were used with the purpose of clarifying their clonal origin and the role of endometriosis in carcinogenesis of endometrioid cancer.
Results. Despite signifi cant differences in the clinical course of the disease and in morphological characteristics of tumors in these two groups of patients, the results of molecular genetic testings have shown that in 100% of observations endometrioid tumors have a common clonal origin and conform to cancer of the uterine corpus with metastases in the ovaries. Analysis of endometriosis foci revealed the decrease of ARIDIA expression in 8 (80%) cases of 10 observations. Conclusion. Based on molecular genetic research conducted, it was shown that endometrioid cancer of uterine corpus and the ovaries represent the same pathology and their occurrence is associated with endometriosis.
Keywords: endometriosis, endometrioid ovarian cancer, cancer of uterine corpus, molecular genetic analysis, ARID1A, К-ras.
 Full text (in Russian)

Objective of the study is to identify the possibility of the diagnosis of benign and precancerous lesions of fallopian tube epithelium using cytological technique by comparing the specifi c features of liquid-based cytology smears and histological preparations.
Materials and Methods: 23 fallopian tubes of 14 patients with high-grade serous ovarian carcinoma (n=6), serous borderline ovarian tumors (n = 7), benign ovarian tumors (n=10) (the mean age of patients was 47,3 ± 13,3 years) were examined using liquid-based cytology, histological, immunocytochemical (bcl-2 expression) and immunohistochemical (p16 and Ki-67 expression) techniques. Criterion χ2 for random number tables was used for statistical processing of the results obtained.
Results. Scanty cellular smears were identifi ed in 48% of cases, moderately cellular smears — in 32%, hypercellular — in 20%. Anisonucleosis was severe in 16% of cases, moderately expressed — в 24%, mildly expressed — in 40%. The distinct roughness of nuclear membrane is observed in 8% of cases, moderate roughness — in 16%, weak — in 40%, roughness was not observed — in 28%. Nuclear chromatin was hyperchromic in 32% of cases, mixed type — in 44%, hypochromic — in 24%. Different types of nuclei was observed in all groups, however, they were more often seen in the group with high-grade serous ovarian carcinoma (in 83%), less often — in the group with benign tumors (in 30%). Nuclei were multiple in 48% of cases, single — in 24%, were not visualized — in 28% of cases. Statistically signifi cant differences were determined in respect of two examined parameters — nuclear polymorphism and the roughness of nuclear membrane which were identifi ed signifi cantly more often in the group with high-grade serous ovarian carcinoma (p < 0,05). Serous tubal intraepithelial carcinoma was detected in all cases in the histological examination of the removed fallopian tubes in the group of patients with high-grade serous ovarian carcinoma (in 43% of cases — in combination with invasive fallopian tube carcinoma), in all cases more than 10 secretory cell outgrowths (SCOUTs) (linear arrays of more than 30 consecutive cells) were detected. In the group of patients with borderline tumors the presence of papillary tubal hyperplasia was revealed in 72% of cases, in 28% of cases — tubal epithelium was unchanged, more than 10 secretory cell outgrowths (SCOUT) were identifi ed in 60% of cases. In the group of patients with benign ovarian tumors the presence of more than 10 SCOUT (secretory cell outgrowths) was found in 20% of cases, in all other cases unchanged tubal epithelium was identifi ed. Therefore, serous tubal intraepithelial carcinomas (STIC) and more than 10 SCOUT (secretory cell outgrowths) were discovered signifi cantly more often in cases of high grade serous ovarian carcinoma, and papillary tubal hyperplasia — in cases of borderline ovarian tumors (p < 0,01).
Conclusion: Thus, our research demonstrated that malignant and benign cells of fallopian tube epithelium can be verifi ed using cytological method, and such precancerous lesions as serous tubal intraepithelial carcinoma (STIC) can be diagnosed as well. This suggests that liquid-based cytology technique can be used for the screening examination of intraepithelial lesions of fallopian tube.
Keywords: serous tubal intraepithelial carcinoma (STIC), serous ovarian carcinoma, liquid-based cytology.
 Full text (in Russian)

Objective of the study: to conduct an analysis of data available in current literature relating to the diagnosis and treatment of pregnant patients with malignant ovarian tumors.
Materials and Methods. The present review covers the data for recent years on the issue under study provided by foreign authors, as well as the results of research carried out by an expert group «Cancer during pregnancy» of European Society of Gynecologic Oncology (ESGO).
Results. The experts have worked out the guidelines on the management of patients with malignant ovarian tumors during pregnancy.
Conclusions. It is necessary to continue the research on the issue in order to develop an algorithm of more accurate diagnostic procedures and optimal tactics of the management of patients with this pathology.
Keywords: pregnancy, malignant tumors, ovarian cancer.
 Full text (in Russian)

Objective is to investigate the prognostic factors and the results of the treatment of patients with malignant ovarian germ cell tumors.
Materials and Methods. An analysis of the data of 163 patients who had undergone the treatment at the Department of Clinical Pharmacology and Chemotherapy of Federal State Budgetary Institution «N.N. Blokhin Russian Cancer Research Center» of the Ministry of Healthcare of the Russian Federation for the period from 1987 to 2015 was carried out.
Results. With a median of observation of 88 months an overall 5-year survival rate of patients with ovarian germ cell tumors was 85%. 5-year survival rate without progression made up 70%. The use of chemotherapy based on modern regimens (BEP/EP) signifi cantly increased the life expectancy of patients (Relative risk 7,1, 95%-confi dence interval 3,06–16,78, p < 0,001). The level of lactate dehydrogenase is an independent prognostic factor that infl uences on overall survival rate (Relative risk 0,95, 95%-confi dence interval 0,91–1,0, p = 0,04), a stage of the disease based on FIGO staging system (Relative risk 2,79, 95%-confi dence interval 1,32–5,91, р = 0,007) and a prognosis based on IGCCCG (ОР 4,83, 95% ДИ 2,25–10,38, р < 0,001) — on 5-year survival rate without progression.
Conclusion. organ-preserving surgery with further performing of chemotherapy based on bep regimen is a standard treatment for ovarian germ cell tumors and it allows to reach a high survival rate of patients. currently one-sided adnexectomy was identifi ed as an optimal volume of surgical treatment of such patients. chemotherapy based on bep scheme is the most effective regimen of drug therapy.
Keywords: ovarian germ cell tumors, chemotherapy, teratoma, dysgerminoma.
 Full text (in Russian)

Objective of the study is to assess oncologic and reproductive results of the use of organ preservation surgery — radical trachelectomy in young patients with invasive cervical cancer.
Materials and Methods. An attempt of organ preservation treatment of invasive cervical cancer performed in the form of radical trachelectomy was undertaken in 167 patients with an average age of 32,3 ± 3,7 years for the period from 2005 to 2016 at P.A. Gertsen Moscow Oncologic Research Institute. Surgery was performed via laparotomy (radical abdominal trachelectomy), vaginal and laparoscopic variants of radical trachelectomy were held in 25 (15%) and 23 (13,8%) of cases respectively. After surgical treatment patients were provided with follow-up care at P.A. Gertsen Moscow Oncologic Research Institute.
Results. An average duration of surgery was minimal in the group of patients who underwent radical abdominal trachelectomy (laparotomy) (210 ± 34 min), maximal — in the group who underwent radical vaginal treachelectomy (260 ± 27 min). Radical vaginal trachelectomy and radical laparoscopic trachelectomy, unlike radical abdominal trachelectomy (laparotomy), were characterized by relatively short-term inpatient hospital stays and low levels of blood loss. There were no reported cases of complications that required surgical correction or that affected the treatment strategy. In 24 (14,4%) cases the results of histological examinations constituted a reason for the conversion of radical trachelectomy to radical hysterectomy or for performing of adjuvant treatment with subsequent loss of reproductive function. The median of follow-up after radical abdominal trachelectomy (laparotomy) was 80 months, after radical vaginal trachelectomy and radical laparoscopic trachelectomy — 25 and 10 months respectively. Recurrent cases were reported in 7 (8,9%) patients from the group who had undergone radical abdominal trachelectomy (laparotomy) and in 1 (5,3%) patient from the group who had undergone radical laparoscopic trachelectomy. The rate of overall survival of patients who had undergone radical abdominal trachelectomy (laparotomy) made up 95%, radical vaginal trachelectomy and radical laparoscopic trachelectomy — 100%. The frequency of occurrence of pregnancy after radical abdominal trachelectomy (laparotomy) was 16,9%, of which 58% reached III trimester. In the group of patients who had undergone radical vaginal trachelectomy pregnancies occurred in 6 (27,3%) patients, four children were born, in the group who had undergone radical laparoscopic trachelectomy — 2 (10,5%) pregnancies.
Conclusion. The results of the study that have been conducted certify that from the oncologic point of view radical trachelectomy is an adequate alternative to radical hysterectomy in young patients with tumors of the cervix which are up to 2 cm in diameter. However, the issues regarding the implementation of reproductive function after organ preservation treatment require further research. It is necessary to develop a set of activities aimed at improving of reproductive outcomes in patients who undergo radical trachelectomy. Progress in this direction can be reached only through establishing closer and productive collaboration among oncologists, obstetricians-gynecologists and reproductive endocrinologist.
Keywords: invasive cervical cancer, organ preservation treatment, radical trachelectomy.
 Full text (in Russian)

Objective of the study is to conduct a systematic analysis of the data available in current literature on precancerous conditions in the vagina.
Materials and Methods. The review comprises the data obtained from foreign and Russian sources found in Pubmed on the subject that have been published over the past 10 years.
Results. The present work summarizes current classifi cation and clinical manifestations of precancerous conditions of vagina, possibilities of diagnosis, as well as the tactics of treatment of patients with vaginal intraepithelial neoplasia.
Conclusion. Although precancer of the vagina is a rare pathology, it is necessary to carry out further research of this issue.
Keywords: vagina, intraepithelial neoplasia, classifi cation, diagnosis, morphology, treatment.
 Full text (in Russian)