[Characteristics of PIK3CA gene mutations in Her2-low breast cancer]. / Kharakteristika mutatsii gena PIK3CA pri rake molochnoi zhelezy s nizkim urovnem ekspressii belka Her2/neu.

BACKGROUND: Mutations in the PIK3CA gene, encoding the catalytic subunit of the PI3K class IA p110α, is a common mechanism of activating of PI3K/AKT/mTOR pathway in breast cancer (BC). The detection of these mutations in patients with hormone-positive Her2-negative BC is of important clinical value, since they are the predictor of the sensitivity of the tumor to the PI3K inhibitor - alpelisib. According to the status of the Her2/neu expression, all patients with hormone-positive Her2-negative BC can be divided into two groups - with low expression of Her2/neu (IHC 1+; 2+, ISH-) and with a complete lack of expression of this protein (IHC 0). OBJECTIVE: Establish whether there are differences of the PIK3CA gene mutations charasteristics in BC with luminal immunophenotype and low expression of Her2/neu in comparison with tumors in which Her2/neu expression is absent. MATERIAL AND METHODS: The presence of PIK3CA mutations was determined using real-time PCR on 96 patient tissues of hormone-positive Her2-negative BC. Commercially available cobas PIK3CA Mutation Kit (Roche) and cobas z480 analyzer were used. RESULTS: PIK3CA gene mutations were detected in 40 of 96 cases studied (41.6%). Most of them were localized in the exons 9 and 20, encoding helicase (p.E542K, p.E545X) or kinase (p.H1047X) domains of PI3K, respectively. The frequency of mutations in the exon 9 (p.E542K+p.E545X) was 2.6 times higher in Her2-low BC compared to tumors in which the Her2/neu expression was absent (p<0.05). There were no statistically significant differences in mutation frequency in the exon 20. CONCLUSION: Statistically significant increase in the frequency of exon 9 mutations of the PIK3CA gene is specific for the group of patients with Her2-low BC. Our results supported the concept of Her2-low BCs as the unique entity and pointed out the need of their further study.

[The role of angiotensin-converting enzyme and angiotensin ii receptors of the second type in the pathogenesis of proliferative diseases of the prostate].

Angiotensin converting enzyme, angiotensin II, angiotensin II receptors of the first and second types represent the "classical" axis of regulation of the renin-angiotensin system. OBJECTIVE: to analyze the role of the components of the renin-angiotensin system in the pathogenesis of proliferative lesions of the prostate glan MATERIALS AND METHODS: The study included 63 patients who underwent transrectal prostate biopsy. The first group consisted of 19 patients with benign prostatic hyperplasia, the second group consisted of 19 men whose prostate cancer was detected during repeated biopsy, the third group consisted of 25 men with prostate cancer detected during primary prostate biopsy. The expression of angiotensin II type II (AT2-R) receptors in prostate tissue was evaluated using primary polyclonal antibodies Angiotensin II Type 2 Receptor and the EnVision FLEX imaging system (Dako, Denmark) according to a standard technique. The activity of angiotensin converting enzyme (ACE) was determined in the secret of the prostate gland, RESULTS: It was found that the activity of ACE in the secret of the prostate gland in proliferative diseases is significantly higher than in the "healthy" prostate. The highest activity of ACE was noted for benign prostatic hyperplasia, and the minimum - for prostate cancer. The expression of AT2-R in prostate tissues in proliferative diseases of the prostate gland has its own characteristics. The expression of AT2-R in the prostate stroma turned out to be the same, in the nuclei of epithelial cells, the level of expression of AT2-R decreased in the range of BPH-PIN-CP. Thus, an increase in the activity of ACE, the accumulation of angiotensin II in prostate secretions in proliferative prostate diseases against the background of a deficiency of AT2-R is the metabolic basis of malignant transformation of the prostate gland. CONCLUSION: The levels of ACE activity in prostate secretion and the expression of AT2-R in prostate tissue during primary prostate biopsy can be considered as promising prognostic tools for early detection of prostate malignancy.

[HER2/neu gene amplification as a mechanism of clonal heterogeneity in breast cancer]. / Amplifikatsiia gena HER2/neu kak mekhanizm vozniknoveniia klonal'noi geterogennosti pri rake molochnoi zhelezy.

OBJECTIVE: To estimate the heterogeneity of HER2/neu gene amplification in HER2/neu-positive breast cancer (BC). MATERIAL AND METHODS: Fluorescence in situ hybridization (FISH) assay was used to estimate HER2/neu gene amplification and HER2/CEP17 ratios in BC samples with an immunohistochemical evaluation of HER2/neu2+ expression. The results were interpreted according to the 2018 ASCO/CAP guidelines. BC samples with HER2/neu gene amplification (n = 25) was evaluated for variability in HER2/neu amplification and HER2/CEP17 ratios in 20 tumor cells counted using the FISH assay. RESULTS: Significant intratumoral variability was found in the HER2/neu gene copy number and HER2/CEP17 ratios. HER2/neu-negative cells (5-15%) were present in 28% of the examined samples found to be HER2/neu positive. The HER2/neu gene copy number and HER2/CEP17 ratios for these tumors were statistically significantly lower than those in the group in which all the counted cells were characterized by HER2/neu amplification: 6.25 (95% CI 4.3-12.45; p=0.0166) and 2.37 (95% CI 2.06-3.43; p=0.0076), respectively. The threshold value of HER2/CEP17, at which cells without amplification were detected in HER2/neu-positive tumors, was 2.5. CONCLUSION: HER2/neu gene amplification in BC is extremely variable both within a single tumor and between the tumors of the same biological subtype. Amplification heterogeneity is statistically significantly more common in HER2/neu-positive BC with a HER2/CEP17 ratio <2.5 and may affect the outcome of the disease and also be important in the choice of treatment policy.

[Role of angiotensin II receptor type 2 in predicting biochemical recurrence in the treatment of prostate cancer].

AIM: To identify markers for predicting aggressive forms of prostate cancer. MATERIALS AND METHODS: The study retrospectively evaluated expression of angiotensin II type 2 receptors (AT2-R) in prostate needle biopsy tissue from patients with and without biochemical recurrence after combined hormone and radiation therapy. RESULTS: The study findings showed that low expression of AT2-R in prostate tissue was associated with a high risk of biochemical recurrence. The data on the nature of AT2-R expression in prostate tissue of prostate cancer patients may be considered as a tool for predicting biochemical recurrence after combined hormone and radiation therapy. The test has a sensitivity of 87.5% and specificity of 85.71%.

[Specific features of gene amplification on the long arm of chromosome 17 in different molecular genetic subtypes of breast cancer].

The frequency of gene amplification and coamplification of HER2/neu, TOP2A and the centromeric region of chromosome 17 (CEP17) was examined in 265 breast cancer (BC) cases belonging to different molecular genetic subgroups. Luminal B breast cancer was found to be characterized by the increased probability of coamplifications (CEP17 and HER/neu, HER2/neu, and TOP2A) on chromosome 17. At the same time, the amplification of just three loci on one chromosome is a rare event and encountered in 17% of luminal B breast cancer cases (or 1.1% of all BC cases). That of HER2/neu in conjunction with elevated CEP17 count is statistically significantly more rarely accompanied by deletion of TOP2A rather than its amplification. The findings suggest that there are different amplification mechanisms in different BC molecular genetic subgroups.

[A FISH analysis in one day. Experience in evaluating HER2 gene status by means of a new HER2 IQFISH pharmdx kit].

Determination of the HER2 status of tumor cells in stomach and breast cancer is a routine diagnostic method. Immunohistochemical study is sufficient for its evaluation in most cases. However, a specifying molecular genetic study using the FISH technique is performed when borderline results are obtained. The paper describes the new procedure IQFISH that allows the results to be obtained in one working day.

[Gene amplification and coamplification in breast cancer: frequency and prognosis value].

Numerical impairments in genes or some genome sites - gene amplifications or deletions - are one of the most frequent genetic mutations occurring in breast cancer. Gene amplifications in breast cancer, their frequency, prognostic value, and the possible role of these disorders in the identification of the subtypes of this heterogeneous disease are considered.

[Different Her-2 status in infiltrative and intraductal components of the breast cancer].

In the article a breast cancer case with different Her2 status in invasive and non-invasive components is described. We emphasize on the importance of knowledge about tumor histology for correct interpretation of FISH Her2-test results.

[HER-2/neu-testing in breast cancer: is the immunocytochemistry competent?].

According to ASCO/CAP guidelines, there are two recommended methods for Her2/neu-testing in breast cancer patients such as immunohistochemistry and fluorescence in situ hybridization. This paper analyses results of alternative immunocytochemical method for Her2/neu detection and its diagnostic pitfalls.

[Bcl-2 as a prognostic factor in different molecular genetic subtypes of breast cancer].

It is well known that breast cancers (BC) are divided into 4 molecular genetic subgroups (luminal A, luminal B, HER2/neu-positive, and triple-negative (TNBC). The purpose of the investigation was to comparatively estimate the pattern of expression of Bcl-2, known as a good prognostic marker of BC, in different molecular genetic subgroups and to study the correlation of this protein with proliferative activity index and genetic aberrations on chromosome 17. The investigation covered 290 samples of invasive ductal BC. Bcl-2 expression was identified in 14% of HER2/neu-positive and TNBC cases while 77% of luminal B tumors and 100% of luminal A ones expressed Bcl-2. Loss of Bcl-2 expression correlated with clinically more aggressive BCs having a high proliferative activity and amplification of HER2/neu and chromosome 17 centromere. This may suggest the poor prognosis of luminal B, HER2/neu-positive and TNBC with no Bcl-2 expression and calls for further investigations on larger samples.

[Diagnostic algorithm in severe acute pancreatitis].

Efficacy of diagnostic algorithm in 164 patients with severe acute pancreatitis based on complex results of ultrasonic examination, esophagogastroduodenoscopy, computed tomography, magnetic resonance pancreatocholangiography and retrograde pancreatocholangiography is analyzed. The results show that this algorithm is highly effective and provides optimal treatment policy, better treatment results and lower lethality in severe acute pancreatitis. Balthazar's score system with calculation of CTSI index in combination with Ranson and Apache II scales raise accuracy of the disease prognosis.