rus
Gynecologic Oncology

Gynecologic Oncology 2019 #1

Content

FUNDAMENTAL ONCOLOGY
Bogush T.A., Basharina A.A., Bogush E.A., Vikhlyantseva N.O., Chemeris G.Yu., Zhordania K.I., Tyulyandina A.S., Tyulyandin S.A.
Estrogen Receptors As Predictors Of The Effectiveness Of Platinum Agents And Taxanes In Patients With Ovarian Cancer
4
Objective of the study is to evaluate the clinical signifi cance of the expression of estrogen receptors of different types (ERα and ERβ) in the prognosis of the effectiveness of platinum- and taxane-based chemotherapy for ovarian cancer.
Materials and Methods. Quantitative assessment of the level of ERα and ERβ expression in ovarian cancer tissue was carried out using fl ow cytofl uorometry technique in a patient cohort (n=31) homogenized by following clinical characteristics: stage III high-grade serous ovarian cancer , non-optimal extent of cytoreduction, 6 cycles of fi rst line platinum- and taxane-based chemotherapy.
Results. ERα and ERβ expression was revealed in all samples of ovarian cancer with signifi cant heterogeneity of quantitative indicators of the markers in different patients and the excess of the median of ERβ expression was 1,5 times as high as the same indicator for ERα. Analyzing Kaplan -Meier curves for progression-free survival , it was evident that the median of progression-free survival was 2 times higher (p = 0,02) and the risk of recurrence was 2,5 times lower (p = 0,04) in the group with high vs low level of ERβ expression.
Conclusion. A high level of ERβ expression in the tumor (in more than 40% of cells) is a predictor of the effectiveness of fi rst line chemotherapy for ovarian cancer based on platinum- and taxane-based agents.
Keywords: estrogen receptors α, estrogen receptors β, ovarian cancer, fl ow cytofl uorometry, chemotherapy, platinum- and taxane-based agents.

 Full text (in Russian)
Nikulitskiy S.I., Tyrsina E.G., Yu.M. Timofeev, Inshakov A.N., Ryabaya O.O.
The New Method Of Measuring The Level Of VEGF-R1 In The Nucleus Of A Cancer Cell Is The Possibility To Evaluate The Degree Of Cell Malignization
10
Objective of the study. The work studied VEGF-R1 and its role in the possibility of the evaluation of the degree of cancer cell malignization.
Materials and Methods. Two lines of human tumor cells A431 and BRO were used as the objects of study. The line of normal human fi broblasts (PHF) served as a control line. The quality of extracted nuclei was assessed based on the criteria of their intactness and purifi cation from cytoplasm. The presence of nuclear markers PCNA and lamin A/C, based on the data of fl ow cytometry (FC), was indicative of preservation of nuclear proteins and the absence of the cytoplasmic β — tubulin confi rmed that that the nuclei did not contain cytoplasmic impurities. After implementation of controls, the content of VEGF- R1 was measured by fl ow cytometry (FC).
Results. The high content of PCNA and lamin A/C in the extracted nuclei with almost complete absence of β — tubulin proved that the protocol might be used to obtain a pure suspension of single intact cell nuclei. The measurement of the nuclear VEGF-R1 content revealed that it was present only in tumor cell nuclei, and that in more malignant BRO cells the receptor content was 1.75 times higher than in A431.
Conclusions. The developed method of extraction of cell nuclei for their subsequent fl ow cytometry analysis was found to be suitable for the quantitative evaluation of protein content in the native nucleus. The presence of VEGF-R1 in the nuclei of tumor cells rather than in normal cells supports the assumption that the nuclear receptor contributes to carcinogenesis. The revealed tendency to increased content of the receptor in the nucleus as the malignancy of cell line increases indicates that the nuclear receptor ‘s level may be used for prognostic purposes. In addition, these results allow to consider VEGFR1 itself as a potential target in anticancer therapy.
Keywords: oncology, Vascular Endothelial Growth Factor Receptor type 1 (VEGF-R1), nuclear extraction, fl ow cytometry (FC), A431 and BRO tumor cell lines, postnatal human fi broblasts PHF.
List of Abbreviations
VEGF-R1 — Receptor Type 1 for Vascular Endothelial Growth Factor
ICC — Immunocytochemistry
IFRFC — Immunofl uorescence Reaction on Flow Cytometer
MFI — Mean Fluorescence Intensity
AB — Antibodies

 Full text (in Russian)
OVARIAN CANCER
Payanidi Yu.G., Zhordania K.I., Khokhlova S.V., Dobrokhotova Yu.E., Shevchuk A.S.
Ovarian Malignant Neoplasms And Pregnancy (Clinical Recommendations ESGO, 2017)
20
Objective of the study is to conduct a systematic analysis of the data available in current literature on the tactics of treatment and management of pregnant women with ovarian malignant neoplasms.
Materials and Methods. The overview comprises the results of international studies , in particular ESGO recommendations on this subject.
Results. The process itself of staging of the disease during pregnancy and treatment must comply with the modern standards to the extent possible. All pregnant patients with ovarian cancer must undergo surgical staging with subsequent chemotherapy. An exception is made for patients with non-clear cell low-grade (G1, G2) ovarian cancer stage IA. In cases of advanced ovarian cancer chemotherapy may be the only treatment that provides an opportunity to preserve pregnancy. Chemotherapy is not prescribed for pregnant patients with early stage non-epithelial ovarian cancer. At advanced stages chemotherapy is performed following the same scheme and regimen as for non –pregnant patients.
Conclusion. It needs to be recognized that ESGO clinical recommendations given above, unfortunately, cannot address all the questions. The gold standard for treatment of pregnant patients with ovarian cancer has not yet been developed. Nevertheless, it is still feasible to follow the proposed option of tactical approaches and to continue research in this direction.
Keywords: malignant ovarian tumors, clinical recommendations, pregnancy.
 Full text (in Russian)
Zhordania K.I., Gokadze N.N., Savostikova M.V., Krasnoschekova G.I., Payanidi Yu.G., Selchyuk V.Yu.
Diagnostic Signifi cance Of p53, p16, WT1 Markers In The Aspirated Material Obtained From The Uterine Cavity In Patients With Serous Ovarian Cancer
28
Objective of the study is to conduct a systematic analysis of the data available in the literature on carcinogenesis of serous ovarian carcinomas, diagnostic signifi cance of their molecular markers and modern possibilities of improving early diagnosis of the disease based on immunocytochemical examination of aspirated material obtained from the uterine cavity.
Materials and Methods. The overview comprises the data from Russian and foreign academic articles published in Pub- Med on the subject over the past 10 years.
Results. The article presents the description of contemporary views on carcinogenesis of serous poorly differentiated ovarian cancer (high-grade, HGSC) and diagnostic methods, as well as it introduces the results of p53, p16, WT1 molecular marker expression in aspirated material obtained from the uterine cavity which promote the diagnosis of the disease.
Conclusion. It is necessary to carry out further research aimed at the development of new possibilities of the diagnosis of ovarian cancer of different morphological types, identifi cation of the predictors of the disease based on immunocytochemical (ICC) method.
Keywords: serous ovarian cancer, serous fallopian tube intraepithelial carcinoma, p53, p16, WT1, aspirated material from the uterine cavity, immunocytochemical method.
 Full text (in Russian)
UTERINE CANCER
Novikova O.V., Avasova Ch.A., Novikova E.G., Krasnopolskaya K.V., Lozovaya Yu.A., Charkhifalakyan A.V.
New Variant Of Hormonal Treatment For Atypical Endometrial Hyperplasia And An Early Endometrial Cancer With Fertility Preservation
36
Objective of the study — is to evaluate the effectiveness of the new variant of hormonal therapy using levonorgestrel — releasing intrauterine system (LR-IUS) mirena and gonadotropin-releasing hormone agonist (GnRH agonist) buserelin.
Materials and Methods. Prospective study was conducted for the period from August 2015 to November 2017 and included 27 patients of reproductive age who underwent conservative hormonal treatment for atypical endometrial hyperplasia (n = 20) and early endometrial cancer (n = 7) using levonorgestrel –releasing intrauterine system (LR-IUS) mirena and buserelin.
Results. The median age at the moment of the beginning of the treatment was 33 years (from 25 to 43 years). Complete response rate in the group of patients with atypical endometrial hyperplasia made up 95% (19/20) and 100% in the group of patients with endometrial cancer (7/7). One patient of 27 didn’t achieve recovery despite the treatment prolonged to 11 months. At the time when oncologic stage was completed only 14 patients (54%) kept their reproductive intentions. Attempts to achieve pregnancy using assisted reproductive technologies were undertaken in 6 patients of 14 (43%). The birth rate was 43% among the patients who had kept reproductive intentions after recovery and 22% among all patients included in the study. The patients were followed up after the termination of treatment for the periods from 6 to 41 months (the median is 23 months). The rates of relapse — free survival made up 96% in 12 months and 88% in 25 months. Recurrence was identifi ed in two patients in 9 and 25 months after the end of the treatment.
Conclusions. The combination of levonorgestrel –releasing intrauterine system (LR-IUS) mirena and buserelin is an effective method of conservative treatment of young patients with atypical endometrial hyperplasia and an early endometrial cancer. For further implementation of reproductive function it is possible to use assisted reproductive technologies . After the end of hormonal treatment due to the risk of recurrence it is recommended that patients must be followed-up on regular basis.
Keywords: endometrial cancer, atypical endometrial hyperplasia, fertility preservation, hormone therapy.
 Full text (in Russian)
СERVICAL CANCER
Gerasimov S.S., Davydov M.M., Nikulichev L.A., Levchenko N.E., Parfenova E.A.
Cardiac Metastases In A Patient With Cervical Carcinoma (A Case Report)
46
Cardiac metastases from uterine cervical carcinoma are very rare and are mostly revealed by autopsy. Literature reports describe only single clinical cases. This group of patients presents no specifi c clinical manifestations of cardiac metastases, and that results in late diagnosis, low effectiveness of antitumor treatment and poor remote results. The paper reports a clinical case study of cardiac metastases in a patient with III-B stage squamous cell cervical carcinoma.
Keywords: cervical carcinoma, cardiac metastases.
 Full text (in Russian)
TUMORS OF THE VAGINA
Kreynina Yu.M., Aksenova S.P., Kaskulova M.Kh., Nudnov N.V.
Optimal Magnetic Resonance Imaging Protocols Of Lesser Pelvis In The Monitoring Of Radiation Treatment And Follow-Up Of Patients With Mass Lesions In The Vagina
54
Objective of the study is the optimization of the protocols of comprehensive MRI exam of the lesser pelvis organs for primary and differential diagnosis of tumor lesions of the vagina of various genesis and localization as well as the estimation of the value of the protocol of multiparametric MRI scan developed for the clinical use in the planning and monitoring of brachytherapy in patients with gynecologic cancer with primary and metastatic lesion of the vagina.
Materials and Methods. 185 complex MRI scans of the organs of lesser pelvis with extended fi eld-of-view were conducted on high fi eld magnetic tomograph Toshiba Vantage Atlas with magnetic fi eld strength of 1,5 Teslas for 119 patients with malignant neoplasms of female reproductive system. The protocol of multiparametric MRI scan included obtaining T2-weighted images in three orthogonal planes, T2-weighted images with suppression of the signal from adipose tissue (T2fat sat), T1-diffusion — weighted images (DWI) and dynamic contrast-enhanced (DCE) imaging. To provide contrast enhancement of the vaginal lumen with the preservation of natural anatomical structure of the organ MRI scan was performed with MRIcompatible intracavitary endovaginal applicator.
Results. Tumor lesions of the vagina were identifi ed in 65 (54,6%) of patients who underwent examination; predominantly involvement of upper third of the vagina and its vaults was detected in 72,4% of patients, including 31% of patients who had recurrent lesion in vaginal stump occurred against the backdrop of post-operative and post-radiation changes of surrounding tissues. MR-semiotics of tumor lesions of different parts of the vagina as a basis for differential diagnosis with post-therapeutic changes was determined. The value of dynamic estimation of diffusion weighted imaging in the assessment of the effectiveness of radiation treatment was studied. Data was obtained on the direct correlation between clinical trials and the percent of tumor diffusion coeffi cient rise.
Conclusions. Optimized protocols of the complex MRI scan of the organs of lesser pelvis with the extended fi eld of scanning and compulsory inclusion of diffusion-weighted images and endovaginal applicator, along with the traditional T2- weighted, T1-weighted, T2-weighted with fat suppression images provide high informative value of the technique in the detection and differential diagnosis of mass lesions in the vagina, as well as currently they are the method, which has no alternative in terms of sensitivity and specifi city, for visualization for the personifi cation of the programs of high precision radiation treatment and further follow-up in patients with gynecologic cancers with primary and metastatic involvement of the vagina.
Keywords: Magnetic Resonance Tomography, cervical cancer, endometrial cancer, vagina, radiation therapy, recurrence.
 Full text (in Russian)
INTERDISCIPLINARY QUESTIONS
Obukhova O.A., Kurmukov I.A.
Selenium In Oncology
66
Objective of the study is to conduct a systematic analysis of the data available in current literature on the therapeutic possibilities of the use of antioxidant selenium in the prevention and treatment of oncologic diseases.
Materials and Methods. The literature overview comprises the data presented in the works written by English language and Russian authors.
Results. The article testifi es the role of selenium in antioxidant system and its signifi cance for homeostasis, analyzes the infl uence of selenium on the course of infectious complications of antitumor treatment and its implication in the prevention of different malignant neoplasms.
Conclusion. It is necessary to carry out further research on the role of selenium in carcinogenesis, its therapeutic implications in comprehensive antitumor therapy. Although the existing fi ndings are encouraging , there is still a great need for additional evidence-based research.
Keywords: selenium, sodium selenite, oncology, antitumor therapy, sepsis.
 Full text (in Russian)
TO US WRITE COLLEAGUES
Vasilieva M.M., Moshurov I.P., Grivtsova L.Yu., Vasiliev M.B.
The Influence Of Immunomodulators On The Course Of Breast Cancer
73
Objective of the study — is to investigate the infl uence of immunomodulators on the course of primary operable breast cancer (PO BC).
Materials and Methods. The research on the infl uence of immunoadjuvant «Polyoxidonium» on the development of medical pathomorphosis of tumor tissue in patients with primary operable breast cancer was conducted.
Results. Medical pathomorphosis of various degree was observed in primary tumor and regional lymph nodes of patients who received Polyoxidonium in neoadjuvant regimen.
Conclusion. The obtained results indicate the possibility of antitumor effect of immunomodulators as well as they call for more in-depth research in this regard.
Keywords: breast cancer, immunoadjuvants, medical pathomorphosis.
 Full text (in Russian)