Objective of the study is to carry out a systematic analysis of the data available in current literature related to general transcriptional, post-transcriptional and post-translational mechanisms of PTEN protein inactivation that are specifi c for endometrial cancer.
Materials and Methods. The review comprises the data of foreign and Russian scholarly articles found in PubMed on the subject, published over the past 10 years.
Results. The recent research indicated that inactivation of tumor suppressor PTEN is a key factor of the development of endometrial cancer. PTEN — phosphatase and tensin homolog — is a signifi cant negative regulator of PI3K-AKT signalling cascade. It inhibits signal transmission by dephosphorylation of phosphatidylinositol-3,4,5- triphosphate (PIP3) to phosphatidylinositol-4,5-biphosphate (PIP2), that lead to the termination of the effects of mitogenic and motogenic stimuli from PI3K. It is well known that the expression and activity of this protein can be regulated both on genetic level and using epigenetic mechanisms. Post-translational modifi cations of this protein can also make their contribution into the regulation of PTEN activity. The present review outlines basic transcriptional, post-transcriptional and post-translational mechanisms of PTEN protein inactivation specifi c for endometrial cancer and prospects of the use of an analysis of its expression for the effective patient stratifi cation.
Conclusion. As PTEN inactivation is specifi c not only for endometrial cancer, but for many other types of solid tumors as well, the study of the mechanisms of the loss of expression of this tumor growth suppressor is a relevant problem of modern molecular oncology and requires further research.
Keywords: endometrial cancer, PTEN
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Objective of the study is to carry out a systematic analysis of the literature data on the use of assisted reproductive technologies, preservation of fertility, on the assessment of the infl uence of pregnancy on the prognosis of the disease in patients with BRCA-associated breast cancer.
Materials and Methods. In order to assess the current state of the problem, a search and analysis of relevant data, published over the past 10 years, was performed in scientifi c databases PubMed, Medline, Elibrary.
Results. Frequency of the carriage of BRCA1/2 gene mutations in patients with breast cancer, diagnosed during pregnancy, methods and results of fertility preservation, safety of subsequent pregnancy in patients with breast cancer who carry mutations in BRCA1/2 genes are described, the necessity of molecular-genetic examination of young patients with breast cancer is justified.
Keywords: breast cancer, BRCA1/BRCA2 genes, mutation, pregnancy, reproduction, fertility
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Disseminated peritoneal leiomyomatosis is a rare disease, which is characterized by peritoneal spread of multiple benign smooth muscle tumors morphologically corresponding to uterine leiomyoma but with unusual localization — outside the genital tract. The cause of the disease is not clear and the possible etiological factors may be related to a hormonal imbalance in females. Although the disease is benign and is characterized by a long duration, many experts classify it as a mesenchymal tumor of unclear malignant potential as a high recurrence rate and an ability to malignant transformation into leiomyosarcoma are common in disseminated peritoneal leiomyomatosis. However, to date there are no clinical guidelines on the management of such category of patients, therefore the treatment of disseminated peritoneal leiomyomatosis can be planned based on the analysis of certain separate clinical observations presented in the world academic literature and drawing on available own experience. The article describes our own experience with treating this pathology, based on a particular clinical case of a patient with disseminated peritoneal leiomyomatosis who wished to preserve reproductive function.
Keywords: disseminated peritoneal leiomyomatosis, tumors of unclear malignant potential.
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Neuroendocrine neoplasia is a group of extremely rare heterogeneous growths, derived from neuroendocrine cells of embryonic neuroectoderm. Neuroendocrine neoplasia affect all organs that have neuroendocrine cells, including the organs of female reproductive system, among which neuroendocrine neoplasia of the cervix, large cell and small cell neuroendocrine cancer in particular, are most commonly diagnosed. A total of 31 studies, including 87 observations of large cell neuroendocrine cancer of the cervix, are documented in the world academic literature. Given the rarity of this pathology, there are currently no specifi c guidelines on the strategy of their treatment, nor there are any retro- and prospective research. The paper provides an overview of literature data over the past 30 years, as well as a clinical observation of a patient with large cell neuroendocrine cancer of the cervix, who underwent treatment at Federal State Budgetary Institution “N. N. Blokhin National Medical Research Center of Oncology” of the Ministry of Healthcare of the Russian Federation.
Keywords: large cell neuroendocrine cancer of the cervix, diagnostics, treatment.
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Immunological characteristics of the tumor have been extensively studied worldwide. It is well known, that phenotypic properties of tumor cells are related to the intricacies of their evolution and their ability to survival under therapeutic effect of the treatment. A substantial prognostic signifi cance of certain tumor phenotypic characteristic features is demonstrated, their predictive role with respect to the effectiveness of immunotherapy is under consideration. Objective: to examine the expression of HLA-determinant, CD71 transferrin receptor in cervical cancer cells and to evaluate tumor lymphoid infi ltration.
Materials and Methods. This study comprised 20 patients with cervical cancer who underwent treatment at Federal State Budgetary Institution “N. N. Blokhin National Medical Research Center of Oncology” of the Ministry of Healthcare of the Russian Federation. The examination of primary tumor was performed using immunohistochemistry technique (immunofluorescence staining) on cryostat sections. Monoclonal antibodies CD45, CD3, CD4, CD8, CD20, CD38, CD71, HLA-DR, HLA-I were used. Assessment of the reaction was carried out using luminescence microscope ZEISS (AXIOSKOP; Germany). Patients with stages IB1 (35,0%) and IB2 (20,0%) predominated in the study.
Results. HLA-class I molecules on tumor cell membranes were expressed in most cases. An absence or expression of this antigen in single tumor cells was observed in 25% of cases. Expression of HLA-class II molecules was evidenced in 55,6% of the examined specimens. In 65,0% (n = 13) of cases CD71 expression was monomorphic, and in 25,0% (n = 5) — mosaic. Lymphocyte infi ltration was expressed weakly, only in 10% of cases (n = 2) focal accumulation of lymphocytes was identifi ed. Plasma cells (CD38+) were found in 20,0% of cases. Histiocytic infi ltration (D11+) was detected in 60% of observations. CD45+ cell infi ltration correlated with the degree of CD3+ (R = 0,459, p = 0,042) and CD8+ (R = 0,505, p = 0,023) cell infi ltration in tumor. The relationship with B-cells, CD38+ cells, D11+ cells was not revealed. CD8+ and CD4+ cell populations were related (p = 0,003).
Conclusion. HLA-class I antigen expression in cervical cancer was preserved in 90,0% of cases. HLA class II antigen expression was noted in 55,6% of observations. Cervical cancer is characterized by a high frequency of transferrin receptor expression even at early stages. Transferrin receptor expression correlated with tumor infi ltration by CD45+ cells. CD45+ cell infi ltration in stroma is more pronounced. The severity of overall infi ltration in tumor tissue in cervical cancer is accompanied by a signifi cant increase of the levels of T-cell infi ltration.
Keywords: cervical cancer, HLA-I, HLA-II, CD71, CD45+ infi ltration, subpopulations, immunofl uorescence, cryostat sections.
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Objective of the study is an analysis of technical and operational characteristics and indicators of diagnostic significance of “NOVAprep-miR-CERVIX” cervical dysplasia severity assessment kit.
Materials and Methods: Cervical epithelium specimens obtained from 226 women (NILM — n.114, HSIL — n.103, CIS — n.9). Methods of the analysis: cytologic examination, histologic examination (for HSIL/CIS specimens), HPV testing, analysis of the expression profi le of six microRNA molecules by reverse transcription technique and polymerase chain reaction (PCR) using “NOVAprep-miR-CERVIX” kit.
Results. Based on biological material quality criteria, a successful analysis of the expression of six microRNA marker molecules was performed in 188 of 226 samples. The value of the miR-CERVIX parameter was calculated for these samples in a range from zero to one. Considering miR-CERVIX threshold value ≥ 0,49, NOVAprep-miR-CERVIX kit can be used for the screening of cervical dysplasia (sensitivity 79%, specifi city 79%). Based on miR-CERVIX threshold value ≥ 0,77, NOVAprep-miR-CERVIX kit can be used for the clarifying diagnosis of severe cervical neoplasia (sensitivity 51%, specifi city 98%).
Conclusion. NOVAprep-miR-CERVIX kit can be recommended for the clinical use as a tool for the assessment of cervical dysplasia severity. Further research is required to determine (a) the rank of NOVAprep-miR-CERVIX technology in the structure of cervical cancer screening programs and (b) the feasibility of the use of this technology for dynamic assessment of cervical dysplasia severity in the process of conservative therapy.
Keywords: micro-RNA, cervical dysplasia, diagnosis, cervical cancer, NOVAprep-miR-CERVIX
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Objective of the study is to carry out a systematic analysis of our own data on the effectiveness of the programs of assisted reproductive technologies (ART) in patients after conservative treatment of atypical endometrial hyperplasia and early stage endometrial cancer.
Materials and Methods. The study comprised 54 women with an initial diagnosis of atypical endometrial hyperplasia (AEH) (n = 28) and early stage endometrial cancer (EC) (n = 26). The comparison group included 50 patients with tuboperitoneal factor of infertility.
Results. Early folliculo- and embryogenesis was compared in patients with atypical endometrial hyperplasia and early stage endometrial cancer after they had undergone conservative treatment within the group and with the control group with tubo-peritoneal factor of infertility, based on the following parameters: the number of mature oocytes, frequency of fertilization, crushing, blastocyst production, as well as the rate of blastocyst production from fertilized oocytes.
Conclusion. It is necessary to carry out further research aimed at the assessment of the outcomes of in-vitro fertilization programs, the improvement of clinical pregnancy rates and the births of healthy babies in assisted reproductive technologies programs for patients after conservative treatment of atypical endometrial hyperplasia and early stage endometrial cancer.
Keywords: atypical hyperplasia, early stage endometrial cancer, embryogenesis, conservative treatment.
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