[Lipidomic markers of breast cancer malignant tumor histological types]. / Lipidomnye markery gistologicheskikh tipov zlokachestvennoi opukholi molochnoi zhelezy.

The molecular profile of a tumor is associated with its histological type and can be used both to study the mechanisms of tumor progression and to diagnose it. In this work, changes in the lipid profile of a malignant breast tumor and the adjacent tissue were studied. The potential possibility of determining the histological type of the tumor by its lipid profile was evaluated. Lipid profiling was performed by reverse-phase chromato-mass-spectrometric analysis the tissue of lipid extract with identification of lipids by characteristic fragments. Potential lipid markers of the histological type of tumor were determined using the Kruskal-Wallis test. Impact of lipid markers was calculated by MetaboAnalyst. Classification models were built by support vector machines with linear kernel and 1-vs-1 architecture. Models were validated by leave-one out cross-validation. Accuracy of models based on microenvironment tissue, were 99% and 75%, accuracy of models, based on tumor tissue, were 90% and 40% for the positive ion mode and negative ion mode respectively. The lipid profile of marginal (adjacent) tissue can be used for identification histological types of breast cancer. Glycerophospholipid metabolism pathway changes were statistically significant in the adjacent tissue and tumor tissue.

[Lipidomic markers of tumor progress in breast cancer patients]. / Lipidomnye markery opukholevoi progressii u bol'nykh rakom molochnoi zhelezy.

Research of cancer progression mechanisms and their impact on metabolism of tumor cells and tumor microenvironment cells is an important element in drug development for cancer target therapy. In this study, changes in tumor tissue and margin tissue lipid profiles, were associated with the following clinical and morphological characteristics: tumor size, cancer stage, multifocalite, tumor grade, number of lymph node metastasis, Nottingham prognostic index, total malignancy score, level of Ki67 protein. Lipid profiling was performed by reverse-phase chromato-mass spectrometry analysis of lipid tissue extract with lipid identification by characteristic fragments. In the lipid profile of tumor tissue 13 characteristic lipids were selected. Their levels significantly correlated with at least 5 clinical and morphological features. Eight of 13 belonged to phosphatidylcholines. In lipid profile of tumor microenviroment tissue 13 lipid features were selected. Their levels significantly correlated with at least 5 clinical and morphological features. Four of 13 belonged to oxidized lipids, 4 lipid features belonged to sphingomyelins, four of 13 belonged to phosphatidylethanolamines. The tumor microenvironment tissue lipid profile correlated with tumor size, cancer stage, tumor grade, number of axillary metastases, Nottingham prognostic index. The tumor tissue lipid profile correlated with tumor size, tumor grade, total malignant score, and number of axillary metastases.

[Immunohistochemical and molecular diagnosis of inflammatory myofibroblastic tumor of the uterus: a literature review and a clinical case]. / Immunogistokhimicheskaya i molekulyarnaya diagnostika vospalitel'noi miofibroblasticheskoi opukholi matki: klinicheskoe nablyudenie i obzor literatury.

Inflammatory myofibroblastic tumors of the uterus (uIMT) are rare and difficult to diagnose neoplasms, since the morphological characteristics of this tumor are not specific and are found in other pathological changes. In addition, until recently, specific uIMT markers have not been identified and their diagnostic standards not defined. However, in recent years, there have been more and more studies aimed to identify characteristic morphological, immunohistochemical, and molecular genetic features for the differential diagnosis of uIMT. Recent papers studying uIMT indicate anaplastic lymphoma kinase (ALK) as a potentially reliable marker of uIMT. This communication describes a clinical case of uIMT in a 40-year-old woman who has been preoperatively diagnosed with a large subserous interstitial myomatous nodule. The final diagnosis was made, by analysing a combination of morphological and immunohistochemical signs. This clinical case with a literature review is indicated to consider ALK as a key criterion in the diagnosis of uIMT, as well as the relationship between subsequent treatment and the presence of ALK in the studied tissues.

[Methylation profiles of genes in breast cancer luminal HER2-negative primary tumor during regional lymphnode metastasis]. / Profil' metilirovaniia genov pervichnoi opukholi u bol'nykh liuminal'nym HER2-negativnym rakom molochnoi zhelezy pri metastazirovanii v regionarnye limfaticheskie uzly.

Aberrant methylation is strongly associated with development of cancer, but limited data exist on correlation between methylation and regional lymph node metastasis (RLNM). The aim of this research was to study using of methylation levels of WIF1, RASSF1A, CDO1 and MEST aberrant methylated genes in a primary breast cancer for prediction of regional lymph node metastases. We used MS-HRM (Methylation Sensitive High Resolution Melting) to assess methylation levels. The results were confirmed by pyrosequencing. The study included 66 women with LumA and 46 women with HER2- (LumB-), 22 and 26 of them had metastasis in at least one lymph node respectively. It was found that methylation levels between LumA and LumB subtypes differed significantly in genes: WIF1 (p<0.001), CDO1 (p=0.002) and MEST (p=0.033). In the Lum A subtype statistically significant differences in level of methylation of WIF1 gene between patients with metastases in RLNM and patients without metastases were found (p=0.03). Analysis of tumors longer than 2 cm in the LumA subtype, revealed an increase of statistical significance of WIF1 gene - p=0.009 (AUC (95%CI) = 0.76 (0.59-0.93)). In LumB- subtype RASSF1A, CDO1 and MEST had statistically significant differences in methylation level between groups (p=0.03, p=0.048 and p=0.045 respectively). ROC analysis showed that combining of three genes by logistic regression, AUC (95%CI) was 0.74 (0.6-0.88). Analysis of tumors longer than 2 cm, did not increase statistical significance for these genes (p=0.046; p=0.089 and p=0.076, respectively). Thus, the study of methylation in primary tumors may be useful for prediction of lymph node metastasis, as well as for better understanding of biological process inside breast cancer.

Expression of micrornas in molecular genetic breast cancer subtypes.

BACKGROUND: It is shown that each type of human malignancies has a unique set of expressed miRNAs, and tumor-specific miRNAs in biological tissues of a patient are stable. The aim of this study was to determine the differences in the expression of miRNAs in tumor tissue of invasive breast carcinoma compared to normal tissue, as well as to analyze the variable expression of miRNAs in molecular genetic subtypes of breast cancer. METHODS: We determined differences in mRNA expression in 35 biopsies of tumor tissue of various molecular genetic subtypes of breast cancer and 35 biopsies of adjacent conventionally normal breast tissue by RT-PCR in real time. We assessed the expression levels of miRNA-21, 221, 222, 155, 205, 20a , 125b and 200a. RESULTS: A significant increase in the level of expression of the oncogenic miRNA-20a (p=0.000141) and miRNA-221 (p=0.037777) in the triple negative cancer in comparison with the luminal A and luminal B/HER2/neu-negative breast cancer subtypes was established. Assessment of significance of the results was conducted using ROC analysis. For miRNA-221 AUC value was 0.772, for miRNA-20a AUC value was 0.949. The obtained results suggest the possibility of using the levels of miRNA-21, 155, 205, 125b expression in tumor tissue to assess a malignant potential of a breast carcinoma. The levels of expression of oncogenic miRNA-221 and miRNA-20a are increased in TNBC compared with luminal A and luminal B/HER2/neu-negative breast cancer subtypes, supporting the characteristic of TNBC as the most aggressive subtype of breast cancer. MiRNA-20a is a marker of TNBC compared with luminal subtypes of breast cancer. MICRO ABSTRACT: To identify markers for breast cancer with triple-negative phenotype, we evaluated expression levels of siRNA-21, 221, 222, 155, 205, 20a, 125b, 200a and 146b in the tumor tissue of 35 patients by RT-PCR. AUC value equal to 0.949 in the ROC-analysis allows us to recommend the miRNA-20a as a marker of triple negative breast cancer to differentiate it from the luminal subtypes.

[NOMOGRAM AS A PROGNOSTIC TOOL FOR LYMPH NODE METASTASIS IN PATIENTS WITH BREAST CANCER].

It was retrospectively analyzed clinicopathological features of 529 breast cancer patients treated at the Ulyanovsk Oncology Center. Of 529 patients 235 (44.4%) had at least one positive axillary lymph node. Tumor size (p = 0,0005), histological grade (p = 0004), lymphovascular invasion (p < 0,0001), HER2-status (p = 0,014) and total score of malignancy (p < 0,0001) were significant independent predictors for lymph nodes metastases. By univariate and multivariate regression analysis it was created the graphic variant of nomogram which could predict the risk of lymph nodes metastases in breast cancer patients. An area under ROC-curve in our nomogram reached 0,737 that demonstrated high prediction level of accuracy of the developed model. Thus new nomogram is a useful tool in planning axillary surgery in breast cancer patients.