Introduction. There is ample evidence that disseminated tumor cells (DTC), which are found in the bone marrow (BM) of patients with breast cancer (BC), including early stages, are progenitors of subsequent distant metastasis. Therefore, BM-DTC represent an additional tool for understanding carcinogenesis and estimating prognosis. Nevertheless, the existing data are controversial. The purpose of the study – to determine the frequency of DTC detection in BM of patients with luminal BC and also its relationship with some clinical and immunophenotypic parameters. Materials and methods. BM bioptates of 65 luminal BC patients were analyzed for the presence of DTC by Attune Acoustic Focusing Cytometer. For the first time in Russia, the sensitivity of the DTC detection method in the BM to the level of 1 × 10–7 myelocaryocytes was increased. Results. In BM, DTC were detected in 40 % of patients, and this finding did not correlate with stage of BC and degree of malignancy. The level of CD8+ lymphocytes in patients with DTC in the BM was significantly lower and amounted to 39,2 % versus 48,1 % in patients without DTC (p = 0,011). The content of myelocaryocytes with DTC-positive status was 1,6 times lower than in the absence of DTC (р = 0,007). Other parameters of the myelogram did not differ significantly. Moreover, no significant correlations were found between the presence of DTC in BM and the breast tumor immunophenotype (HLA-I: p = 0,74; HLA-DR: p = 0,93; CD71: p = 0,46). Conclusion. The presence of BM-DTC is more interrelated with myelogram and subpopulation of BM lymphocytes than with the clinical characteristics of tumor.

Currently, mammography is the main screening method for diagnosing breast cancer (BC); but the process of carcinogenesis begins long before the appearance of a visualized tumor. For successful early diagnosis of breast cancer, a systematic approach is required, that includes all stages of tumor development. On the example of BC we consider the possibilities of integrating the recent scientific achievements of oncogenetics and proteomics with standard methods. In this article we investigate the possibilities of using genetic research, serum cancer markers and radiation methods for early diagnosis of BC. This article also presents potential options for managing high-risk development of this disease.

Роль метилирования генов микроРНК в различных молекулярно-биологических подтипах рака молочной железы Злокачественные опухоли www.malignanttumours.org

Breast cancer (BC) is the multifactorial disease where different genes play the major pathogenic role with tumor-suppressor genes in particular. These genes methylation is supposed to be the common regulation mechanism. The aim of the present paper is to study methylation in group of tumor-suppressor genes: RASSF1A, SEMA3B, RARP2, RHOA, GPX1 and NKIRAS1 in luminal and mioepithelial breast cancer, and to evaluate their correlation with clinical subtype's course of this disease. Methods. Analysis of methylation was done in group of 174 malignant/normal breast tissue pairs and of 10 health breast tissue samples. Two independent methods a methyl-specific PCR (RASSF1A, RARP2, SEMA3B) and methylation-sensitive restriction analysis (RHOA, GPX1, NKIRAS were used. Results. A statistically significant high methylation frequency for genes RASSF1A, SEMA3B and RAR-p2 were shown (the positive ratio ranged from 13.2% to 37.9%) compared with normal breast tissue (the positive ratio ranged 0-6.9%, respectively), (p<0.00001). We revealed high frequent methylation level of RAR-P2 gene that was significantly higher in the luminal subtype B with the over expression of Her2 and Ki-67 compared with Her2-negative type and low level of Ki-67 (44% vs. 23.1%, p = 0.0458 and 38.5% vs. 16.2%, p = 0.0059, respectively). Interestingly we report that 5 and 10 years survivability without methylation was 93.5%, 85.5%, and 91.3%, 83.7%, respectively, compared ones with methylation where was lower 80.3 %, 65.3% (p = 0.007) and 84.3%, 67.2% (р=0,038) respectively. Conclusion. Methylation of RASSF1A, SEMA3B, RAR-P2, GPX1, RHOA и NKIRAS1 genes plays important role in tumorigenesis of luminal breast cancer by modulating their functions. Methylation of the RASSF1A and RAR-P2 genes is associated with an unfavorable the disease outcome. Identified epigenetic alterations in luminal subtypes BC could be included in the biomarker system to improve in evaluating diagnosis, prognosis of disease, especially for choosing the individual tactics of treatment.

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