Aim. Analysis of the diagnostic and prognostic potential of a group of microRNA genes hypermethylated in epithelial ovarian cancer (EOC).
Materials and methods. Paired samples (tumor and conditional norm) obtained after the surgery of 54 patients with morphologically diagnosed ovarian epithelial tumors were studied. Methylation status was determined using bisulfi te DNA conversion and subsequent methylation-specifi c PCR.
Results. Most of the studied samples showed aberrant methylation in 8 miRNA genes. The comparison of the data on the methylation of these genes in 54 paired patients’ samples and 18 donors (who died from non-cancer diseases) samples made it possible to determine a set of 4 markers (MIR-107, -124-3, -129-2, -193a) that have diagnostic potential. According to the ROC analysis, this set of markers makes it possible to diagnose EOC in patients’ biopsy samples with a high clinical sensitivity of 87% and a specifi city of 100%, AUC = 0.936. In accordance with the clinical and histological characteristics, 54 samples of EOC were divided into two groups: 37 samples without metastasis and 17 samples with metastasis to regional lymph nodes or distant organs. The methylation of the 5 genes (MIR-1258, -129-2, -137, -193a, -203a) is signifi cantly associated with metastasis and allows us to differentiate these two groups of patients. According to ROC analysis, this set of markers can predict metastasis with a clinical sensitivity of 94% and a specifi city of 81%, AUC = 0.892. In accordance with the characteristics of this system, it is necessary to establish methylation of 3 out of 5 markers of this system for the prognosis of metastasis of EOC. Conclusion. The proposed markers’ set based on methylation of a group of microRNA genes can be use in clinical oncology after its validation.
Keywords: epithelial ovarian cancer, microRNA, methylation, metastasis, markers.
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Objective of the study is to demonstrate the influence of sympathetic nervous system on carcinogenesis in patients with gynecologic cancers.
Materials and methods. An analysis of current studies on the infl uence of sympathetic nervous system on tumor progression has been performed.
Results. Experimental and clinical studies identifi ed the mechanism of direct correlation between stress experienced by patients and tumor progression. Under stress activation of sympathetic division of peripheral nervous system occurs. Activation of sympathetic nerve fi bers located in tumor tissue, results in the increase of catecholamine concentration in it. Catecholamines binding to beta-adrenergic receptors of tumor cells and cells of tumor microenvironment , modulate expression of genes of malignant tumor, which, in turn, induces tumor growth and metastasis through stimulation of angiogenesis and formation of new lymphatic vessels.
Conclusion. Activation of sympathetic nervous system leads to the stimulation of carcinogenesis in patients with gynecologic malignancies.
Keywords: carcinogenesis, stress, sympathetic nervous system.
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Objective of the study is to assess the relationship between bone marrow effectors of innate immunity and clinical parameters in operable breast cancer as well as in benign breast tumor diseases.
Materials and methods. The paper presents the data on the composition of cells of innate immunity in bone marrow of 64 patients with operable breast cancer and 10 women with benign breast diseases.
Results. Reliable correlation between molecular subtypes of cancer and the level of B1-lymphocytes was revealed. No such pattern was observed for TCRγδ-lymphocytes. A relationship between plasma cells and B1-lymphocytes was also identifi ed. Conclusion. The relationship between effector subpopulations of innate immunity in bone marrow and the course and prognosis of breast cancer exists and requires further investigation.
Keywords: breast cancer, TCRγδ-cells, B1(CD5+)-lymphocytes, haematopoiesis.
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Objective of the study is to provide up-to-date information on the meaning, classifi cation, pathogenesis and diagnosis of endometrial hyperplasia as well as to conduct a systematic analysis of data available in the literature on the possibilities of the use of immunohistochemical markers in diagnosis of atypical hyperplasia and endometrioid adenocarcinoma of the endometrium.
Materials and methods. The review comprises data obtained from foreign and Russian academic articles found in PubMed on the subject published over the past 20 years.
Results. The article describes potential immunohistochemical markers of malignant transformation of endometrial hyperplasia.
Conclusion. Further research is required in this fi eld to create prognostically signifi cant diagnostic panel of immunohistochemical markers for the verifi cation of morphologically challenging diagnosis of atypical endometrial hyperplasia and to determine the risk of malignization of endometrial hyperplasia.
Keywords: endometrial hyperplasia, endometrial cancer, endometrioid neoplasia of the endometrium, malignant transformation of endometrial hyperplasia.
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Objective of the study is to carry out a systematic analysis of the data available in current literature and to investigate how often promoter hypermethylation occurs in patients with breast and ovarian cancers, in carriers of BRCA1 and BRCA2 genes germline mutations, as well as to determine the relevance of the analysis of BRCA1/2 promoter hypermethylation for implementing it into clinical practice.
Materials and methods. The review comprises the data obtained from foreign and Russian scholarly articles found in PubMed on the subject, published over the past 10 years.
Results. Analysis of international literature revealed that BRCA promoter methylation in patients with BRCA-associated breast and ovarian cancers occurs rarely, though is somewhat more common in breast cancer and varies at CpG sites.
Conclusion. Analysis of BRCA methylation can be used as cost-effi cient preliminary screening for exclusion of germline BRCA genes mutations and as a marker for prediction of sensitivity to platinum-based agents and PARB inhibitors, as well as for the prognosis of ovarian cancer survival.
Keywords: mutations, promoter hypermethylation, BRCA1/2 genes, ovarian cancer, breast cancer/
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Objective of the study is to establish the rate of errors in precancerous conditions and cervical cancer diagnosis made at different steps of diagnostic process-examination and staging after an initial visit and assessment at a clinic.
Materials and methods. The study comprised 410 patients, who had undergone examination at out-patient clinic of P.A. Gertsen Moscow Scientifi c Research Oncology Institute — a Branch of Federal State Budgetary Institution «National Medical Research Center of Radiology» of the Ministry of Healthcare of the Russian Federation. Patients for examination were selected from archive records and the results of diagnosis were traced back to the moment of primary clinical diagnosis made by a physician at the initial assessment at a clinic (1), after protocol-based examination (2), and, then after surgical staging (3). Statistical analysis of the results was conducted by the Python Programming language tools (Python 3.8. Anaconda). Built-in functions from module Statsmodels and SciPy were used for calculations. Statistical hypothesis testing was performed based on non-parametric Z-test for the difference between two proportions in dependent samples. A linkage analysis for binary traits was conducted based on Matthews correlation coeffi cient. Statistical signifi cance of the difference of Matthews correlation coeffi cient from zero was tested based on the Chi-squared criterion. The differences were considered statistically signifi cant at p < 0,05 (two-sided criterion) and p < 0,025 (one-sided criterion).
Results. The accuracy of diagnosis of precancerous conditions and cervical cancer is far from being perfect and with FIGO staging makes up 42,2% at initial assessment at a clinic. Performing of complete clinical examination, including medical imaging techniques, improves the accuracy of staging only up to 51,2%. At the initial diagnostic assessment metastases in pelvic regional lymphatic nodes are not diagnosed in every 4-th patient (N criterion by FIGO), (underdiagnosis of 24,9%).
Conclusion. The error rate in the diagnostic transition process involving steps «Initial diagnostic assessment — Diagnosis after surgical staging»(1/3) and «Diagnosis after examination — Diagnosis after surgical staging» (2/3) is decreasing. Errors in FIGO staging are most commonly associated with determining T and N factors. Underdiagnosis occurs more frequently than overdiagnosis. While even with T-staging errors the initial method of treatment is usually determined correctly, patients with unidentifi ed metastases in pelvic lymph nodes do not get the right initial treatment according to clinical guidelines.
Keywords: cervical cancer, cancer incidence, cancer diagnosis, cancer stage, diagnostic errors.
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Objective of the study is to present the results of a screening program for cervical cancer in the Republic of Kazakhstan from 2008 to 2016.
Materials and methods. Cervical screening of cervical cancer in the Republic of Kazakhstan was included in the system of mass preventive examinations in 2008. The total number of women screened for 9 years (2008–2016) was 4,460,320 women. Over this period, a decrease in target coverage by screening is noted by 27%: from 72,9% in 2008 to 45,9% in 2016. The highest coverage rate was recorded in 2012 and amounted to 76,8% of the target group.
Results. The increase in the incidence of cervical cancer in the framework of the screening program for 9 years amounted to 37%. Over the study period, there has been an increase in the registration of cases of precancerous pathology of the cervix from 0,136% to 0,673% of the total number of women examined during cervical cancer screening. For the period 2011–2016, an increase in the detection of cases of cervical cancer of the I–II stages was noted: from 88,7% in 2011 to 93,8% in 2016. An analysis of the indicators for identifying advanced stages of cervical cancer during cytological screening showed signifi cant differences for the study period. There is a decrease in cases of stage III cervical cancer detection from 10,1% in 2011 to 5,3% in 2016. The proportion of cases of cervical cancer of stage IV was 1,2% in 2011 and 0 in 2016.
Conclusion. Analysis of cervical screening for 2008–2016 showed a decrease in the target coverage of the female population in the age group of 30–60 years by 27% due to insuffi cient circulation of women. The ongoing screening program allowed to increase the detection rates of patients with precancerous pathology and cervical cancer in the early stages, as well as reducing the incidence of advanced forms. There remains the need for active educational work with the population at different levels, in order to attract young women to annual preventive examinations.
Keywords: screening, screening program, cervical cancer.
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Objective of the study is to determine prognostic possibilities of magnetic resonance imaging (MRI) in women with common pelvic cancers.
Materials and methods. Retrospective analysis of 530 MRI studies of female pelvic organs that were performed on magnetic resonance imaging scanners with magnetic fi eld induction of 1,5 T, was conducted. All patients were divided into two groups: group I — patients with cancer pathology 50% (n = 165), group II — non-tumor pathology 50% (n = 165). Group I of patients with pelvic cancers included cervical cancer, endometrial cancer, ovarian cancer and colorectal cancer.
Results. Intra-group comparison of MRI-data in the investigation of pelvic pathology in females using dispersion analysis ANOVA was carried out. The improvement of patients’ health condition differed between all groups, p = 0,0001. In multifactor regression analysis it was found that the perifocal infi ltration area reduced the probability of improving patient’s condition by a factor of 6, infl ammatory changes — by a factor of 5,2, cervical cancer — by a factor of 4. Deterioration of patients’ condition also varied signifi cantly between groups, p = 0,0001. Multifactor regression analysis revealed that the probability of deterioration of condition was decreased by 78% in the group of non-tumor pathology, increased by a factor of 9,2 by the presence of the main focus showing restricted diffusion, and by a factor of 16,5 by perifocal infi ltration area displaying restricted diffusion, and the value of diffusion coeffi cient measured from the area of perifocal infi ltration reduced the probability of deterioration of condition by 79%.
Conclusion. Diffused-weighted imaging increases diagnostic accuracy and prognostic signifi cance of magnetic resonance imaging (MRI) in female pelvis pathology. The assessment of the area of perifocal infiltration in intravenous contrast administration doesn’t affect the prognostic accuracy of the technique (p>0,05).
Keywords: Magnetic Resonance Imaging (MRI), diffusion-weighted imaging, contrast administration, perifocal infi ltration, cervical cancer, endometrial cancer, ovarian cancer, colorectal cancer.
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Objective of the study is to conduct an analysis of the data available in current literature on the therapeutic possibilities of the use of novel physiotherapy treatment techniques in the correction of psychosomatic depression in gynecologic oncology.
Materials and methods. Literature review comprises the data from English-language and Russian authors on the subject. Results. The paper assesses relevance of the problem of psychosomatic depression in oncology, as well as presents the current data on the possibilities of rehabilitation of cancer patients using novel physiotherapy techniques (transcranial magnetic stimulation), discusses their effectiveness and safety.
Conclusion. It is necessary to carry out further research on the infl uence of transcranial magnetic stimulation on carcinogenesis, as well as continue studies of therapeutic possibilities of the technique, as the use of integrated program of enhanced recovery, combining the methods of physical, psychosocial and pharmacological rehabilitation and tailored to the individual patient — is the future of medical rehabilitation.
Keywords: oncology, gynecologic oncology, castration syndrome, transcranial magnetic stimulation.
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