[Comparative immunohistochemistry study of different antibodies clones for detection of breast cancer markers (estrogen receptor, progesterone receptor, HER2/neu, Ki-67)]. / Sravnitel'noe issledovanie antitel razlichnykh klonov dlya vyyavleniya markerov raka molochnoi zhelezy (retseptorov estrogenov, progesterona, HER2/neu, Ki-67) immunogistokhimicheskim metodom.

OBJECTIVE: A comparative study of detection of breast cancer markers (estrogen receptors, progesterone receptors, HER2/neu, Ki-67) by immunohistochemical method with antibodies produced by PrimeBioMed (Russia) and antibodies produced by Roche Ventana (USA). MATERIAL AND METHODS: Surgical specimens and biopsies from 37 patients with invasive breast cancer were used. Sections were stained with antibodies of clones ER SP1 and GM030, PR 1E2 and PBM-5B8, HER2/neu 4B5 and PBM-46A6, Ki-67 30-9 and GM010. RESULTS: There was a high positive and significant correlation between the immunohistochemistry results and antibodies of the clones ER-SP1 and GM030, PR1E2 and PBM-5B8, HER2/neu4B5 and PBM-46A6, Ki-67 30-9 and GM010. CONCLUSION: The study showed the possibility of using antibodies of clones GM030, HER2/neu 4B5, PBM-46A6, GM010 (PrimeBioMed) on the Ventana Bench Marck Ultra automatic immunostainer using the detection system UltraView Universal DAB Detection Kit.

[Relationship between PD-L1 expression and tumor stem cell marker CD44 as a promising basis for the development of new approaches to cancer targeted therapy]. / Svyaz' mezhdu ekspressiei PD-L1 i markerom opukholevykh stvolovykh kletok CD44 kak perspektivnaya osnova dlya razrabotki novykh podkhodov k targetnoi terapii novoobrazovanii.

Immunotherapy of malignant tumors is a rapidly developing area of oncology. PD-1 is a receptor expressed by activated T-lymphocytes. As a result of its interaction with the ligand (PD-L1 or PD-L2), the activity of T-lymphocytes is inhibited and their apoptosis occurs. Drugs that inhibit the interaction of PD-1 with ligands have an immunostimulatory effect and are effective in the treatment of many types of neoplasms: melanoma, lung cancer, bladder cancer, stomach cancer, various lymphomas, etc. However, response to this treatment is observed only in a narrow cohort of patients. To increase the effectiveness of immunotherapy, combined preparations and nanoparticles are being developed and created to enhance the effect of PD-L1 inhibitors, and containing hyaluronic acid as a ligand for the CD44 protein, which is expressed in many human tumors. However, the issue of co-expression of CD44 and PD-L1 remains poorly understood. This review is devoted to describing the features of co-expression and the mechanisms of interaction between CD44 and PD-L1. Promising directions for the development of new approaches to the immunotherapy of malignant tumors are presented.

Automated Assessment of the Area of Infiltration by CD8+ Cells in Gastric Carcinoma and Areas of Normal Mucosa as a Significant Prognostic Factor.

In 139 patients with verified gastric cancer, the infiltration of the postoperative material with CD8+ cells was analyzed. Automated morphometric analysis of immunostained slides was performed separately in different specimen sites (tumor center, invasive edge, and peritumoral mucosa). The mean area of infiltrating CD8+ cells in the tumor center and in the invasive edge was not predictive, while in the peritumoral mucosa it provided a new negative predictive factor (hazard ratio 2.10; confidence interval 0.87-4.92, Cox regression) reliably associated with the TNM stage (hazard ratio 1.91; confidence interval 0.91-4.61, Cox regression).

[Prognostic significance of PD-L1 expression as a potential predictor of survival in gastric cancer]. / Prognosticheskaya znachimost' ekspressii PD-L1 kak potentsial'nogo prediktora vyzhivaemosti pri rake zheludka.

BACKGROUND: Currently, PD-L1 expression in patients with tumors of various localizations is being actively studied. Studies on the expression of PD-L1 detected by clones SP142 and SP263 in gastric cancer (for the drugs atezolizumab and durvalumab, respectively) are rare in the literature. The prognostic role of PD-L1 expression in patients who were not treated with immune checkpoint inhibitors has also not been investigated. OBJECTIVE: To determine the expression level of PD-L1 (clones SP263 and SP142, Roche Ventana) in gastric cancer specimens and evaluate its effect on overall survival in patients who did not receive adjuvant therapy with immune checkpoint inhibitors. MATERIAL AND METHODS: The study included 131 patients with a verified diagnosis of gastric cancer. The material obtained from 127 patients was stained with antibodies to PD-L1 SP263, and from 126 patients - with antibodies to PD-L1 SP142. A multivariate Cox regression model with Wald's step-by-step exclusion algorithm was used to evaluate predictors of survival. RESULTS: The total five-year survival rate of patients in the PD-L1-negative tumor group was significantly lower than the total five-year survival rate of patients in the PD-L1-positive tumor group, which was 50.0% and 40.0% also for both clones (p=0.027). An increase in the expression of PD-L1 clone SP263, determined by both the CPS and TPS method, reduces the chances of death by 1.35 times (p=0.02) and 1.61 times (p=0.004), respectively. An increase in the expression of PD-L1 clone SP142, determined by the CPS method, reduces the chances of death by 1.54 times (p=0.005). CONCLUSION: The survival rate of patients in the group of PD-L1-positive tumors is significantly higher than in patients in the group of PD-L1-negative tumors. Elevated PD-L1 expression, as assessed by the SP263 and SP142 clones, is an important prognostic marker that predicts a higher chance of overall survival for patients, even though these patients are not receiving immune checkpoint inhibitors adjuvant therapy.

[E-cadherin: structure and functions, role in gastric cancer carcinogenesis]. / E-kadgerin: stroenie i funktsii, rol' v kantserogeneze raka zheludka.

This review is dedicated to E-cadherin, a calcium-dependent cell-cell adhesion molecule with pivotal roles in epithelial cell behavior, tissue formation, and carcinogenesis. We summarize the structure of the E-cadherin, its role in the development of the body and in the carcinogenesis. The structure of the E-cadherin/ß-catenin/αE-catenin complex and its relationship with the actin cytoskeleton are described in detail. The role of E-cadherin in the development of some infectious diseases, the function of E-cadherin as both a tumor suppressor and a promoter of tumor dissemination, its influence on signal transduction pathways in cells are highlighted. Particular attention is paid to the expression of E-cadherin in Helicobacter pylori infection and in tumor tissue in gastric cancer.

Pilot ex vivo study on non-thermal ablation of human prostate adenocarcinoma tissue using boiling histotripsy.

Focused ultrasound technologies are of growing interest for noninvasive ablation of localized prostate cancer (PCa). Here we present the results of the first case study evaluating the feasibility of non-thermal mechanical ablation of human prostate adenocarcinoma tissue using the boiling histotripsy (BH) method on ex vivo tissue. High intensity focused ultrasound field was generated using a 1.5-MHz custom-made transducer with nominal F#=0.75. A sonication protocol of 734 W acoustic power, 10-ms long BH-pulses, 30 pulses per focal spot, 1 % duty cycle, and 1 mm distance between single foci was tested in an ex vivo human prostate tissue sample containing PCa. The protocol used here has been successfully applied in the previous BH studies for mechanical disintegration of ex vivo prostatic human tissue with benign hyperplasia. BH treatment was monitored using B-mode ultrasound. Post-treatment histologic analysis demonstrated BH produced liquefaction of the targeted tissue volume. BH treated benign prostate parenchyma and PCa had similar tissue fractionation into subcellular fragments. The results of the study demonstrated that PCa tumor tissue can be mechanically ablated using the BH method. Further studies will aim on optimizing protocol parameters to accelerate treatment while maintaining complete destruction of the targeted tissue volume into subcellular debris.

Detection, Role and Prognostic Value of Cancer-associated Fibroblasts in Colorectal Cancer.

Cancer-associated fibroblasts (CAFs) - mesenchymal cells in the tumor stroma, play one of the leading roles in tumor progression in many different tumors, including colorectal cancer. Scientists have described many markers for CAFs, but none of them is specific. We performed immunohistochemistry tests using five antibodies (αSMA, POD, FAP, PDGFRα, PDGFRß) to investigate CAFs in three zones of 49 colorectal adenocarcinomas: apical, central, and invasive edge. We revealed the reliable correlation between high PDGFRß and PDGFRα value in the apical zone and deeper invasion (T3-T4) (p = 0.0281 and p = 0.0137). High αSMA level in apical zone (p = 0.0001), αSMA level in central zone (p = 0.019), POD level in apical zone (p = 0.0222), POD level in central zone (p = 0.0206) and PDGFRß level in apical zone (p = 0.014) correlated reliably with the presence of metastasis in lymphatic nodules. For the first time, focused on the inner layer of CAF adjacent to tumor complexes. We observed that cases with inner αSMA expression were significantly more often (p = 0.023) characterized by the presence of regional lymph node metastasis compared with cases with mix of CAF markers (p = 0.007) and with cases with inner POD expression (p = 0.024). The found relationships between the level of markers and the presence of metastases indicate their clinical significance.

[Mucins expression in gastric cancer: connection of MUC status with clinical, morphological and prognostic characteristics of the tumor]. / Ekspressiya mutsinov v rake zheludka: svyaz' MUC-statusa s kliniko-morfologicheskimi i prognosticheskimi kharakteristikami opukholi.

OBJECTIVE: Clarification of the prognostic value and relationship of MUC-phenotypes of gastric cancer with clinical and morphological parameters. MATERIAL AND METHODS: Surgical material from 310 patients with a verified diagnosis of gastric cancer was studied. Samples were immunohistochemically stained with antibodies to MUC2, CD10, MUC5AC. The results were compared with clinical and morphological characteristics of gastric cancer and patient survival data. RESULTS: The MUC-null and MUC-mix groups significantly differ in the prevalence of subtotal/total tumors from the MUC-I group (p=0.022 and p=0.007, respectively), where there are significantly fewer such tumors. Tubular tumors were more common in the MUC-null group compared to the MUC-G (p=0.026) and MUC-mix (p=0.006) groups, and there were fewer cases with the presence of "signet-ring" cells in the MUC-null group (p=0.000). When studying the discohesive histological type, the literature data on smaller tumor sizes and a lower frequency of lymph node metastasis for MUC-G status were not confirmed, but a more frequent proximal localization of MUC-I tumors was found (p=0.003). No statistically significant differences in survival were found in the analysis of the total sample. Differences in survival were found only in discohesive cancers, where the best survival was recorded for the MUC-null group, and the worst for the MUC-mix group (p=0.022). MUC status is not an independent predictor of gastric cancer (HR=1.662, p=0.093). CONCLUSION: Between tumors with different MUC statuses, there were differences in localization and belonging to individual histological types. Significant differences in survival were found only for discohesive cancers with MUC-null and MUC-mix statuses. Separation of gastric cancers according to MUC status may have only limited predictive value in selected histological forms of cancer.

[Microsatellite instability in gastric cancer is a predictor of a favorable prognosis]. / Mikrosatellitnaya nestabil'nost' v rake zheludka ­ prediktor blagopriyatnogo prognoza.

OBJECTIVE: Evaluation of the frequency of microsatellite instability in gastric adenocarcinomas in patients of the Russian Federation, determination of the relationship of microsatellite instability with clinical and morphological characteristics and the impact on the prognosis. MATERIAL AND METHODS: We used samples of surgical material from 310 patients with a verified diagnosis of gastric cancer. The age of the patients ranged from 22 to 85 years (mean 63 years). The median follow-up of patients was 83 months. Each sample was immunohistochemically stained with antibodies to microsatellite instability markers MLH1, MSH2, MSH6, and PMS2. The results were compared with the main clinical and morphological characteristics of gastric cancer and data on patient survival. RESULTS: The frequency of detection of MMR-negative tumors in the Russian population is 8.1% of all patients with gastric cancer. It was found that patients with MMR-negative gastric carcinomas are older (mean age 69 years, p=0.008). In this group predominates distal localization of tumors, type 2 according to R. Bormann classification (p=0.010), tubular histological type (p=0.010), intestinal subtype according to P. Lauren classification (p=0.003). There were no significant differences between MMR-negative and MMR-positive tumors in terms of other clinical and morphological parameters (including the stage of the tumor process). The overall median survival of patients with MMR-negative tumors was 76%, which significantly (p=0.013) exceeds that in the group of MMR-positive tumors (36%). It was found that despite significant differences in survival, MMR-status is not an significant prognostic factor in gastric cancer (HR=0.983). CONCLUSION: The established differences in patient survival make it possible to distinguish a group of MMR-negative tumors into a separate pathogenetic subtype of gastric cancer (MSI subtype) based on immunohistochemical studies. This subtype occurs predominantly in elderly patients with tubular gastric adenocarcinomas and is characterized by a favorable prognosis.

[Multiplex fluorescent imaging of cancer-associated fibroblasts in colorectal cancer]. / Mul'tipleksnaya flyuorestsentnaya vizualizatsiya opukholeassotsiirovannykh fibroblastov v kolorektal'nom rake.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are a heterogeneous cell population in the tumor stroma and have important prognostic and clinical significance for solid tumors, including colorectal cancer. The identification of CAF presents difficulties due to the lack of a unique diagnostic marker. OBJECTIVE: Detection of CAF by multiplex immunohistochemical staining and assessment of their colocalization. MATERIAL AND METHODS: For multiplex IHC staining specimens of 10 colon adenocarcinomas without neoadjuvant treatment were selected. We used «OPAL 7-COLOR MANUAL IHC KIT¼ (Akoya Biosciences, USA) with five antibodies (FAP, PDGFRß, CD31, POD, PCK) for staining and Mantra 2 Quantitative Pathology Imaging System (Akoya Biosciences, USA) for evaluation of results. RESULTS: CD31 and CAF markers (FAP, PDGFRß, POD) are expressed fundamentally in different cells (p<0.0001) in all areas of the tumor (apical, central, invasive margin). Pairs FAP+PDGFRß in all zones demonstrated significantly higher (p<0.0001) square of tandem staining. It shows that these markers are expressed in the same stromal cells (probably CAF). In pair FAP+POD significant colocalization (p=0.011) was detected only in apical zone. We connect this finding rather with active proliferation of population of young fibroblasts in zones of ulceration and granulations than with CAF. CONCLUSION: We evaluated co-localization of CAF markers (FAP, PDGFRß, POD) and endothelial cells (CD31) in different zones of colorectal carcinomas. We showed colocalization of CAF markers for pairs FAP+PDGFRß in all tumor zones and for pair FAP+POD in apical zone.

[Correlations between vessel stiffness and biomarkers of senescent cell in elderly patients].

Aim    To study the association between vascular wall stiffness and known markers for accumulation of senescent cells in blood, cells, and tissues of old patients.Material and methods    This study included male and female patients aged 65 years and older who were referred to an elective surgical intervention, that included a surgical incision in the area of the anterior abdominal wall or large joints and met the inclusion and exclusion criteria. For all patients, traditional cardiovascular (CV) risk factors and arterial wall stiffness (pulse wave velocity, PWV) were evaluated. Also, biomaterials (peripheral blood, skin, subcutaneous adipose tissue) were collected during the surgery and were used for isolation of several cell types and subsequent histological analysis to determine various markers of senescent cells.Results    The study included 80 patients aged 65 to 90 years. The correlation analysis identified the most significant indexes that reflected the accumulation of senescent cells at the systemic, tissue, and cellular levels (r>0.3, р<0.05) and showed positive and negative correlations with PWV. The following blood plasma factors were selected as the markers of ageing: insulin-like growth factor 1 (IGF-1), fibroblast growth factor 21 (FGF-21), and vascular endothelium adhesion molecule 1 (VCAM-1). A significant negative correlation between PWV and IGF-1 concentration was found. Among the tissue markers, P16INK, the key marker for tissue accumulation of senescent cells, predictably showed a positive correlation (r=0.394, p<0.05). A medium-strength correlation with parameters of the 96-h increment of mesenchymal stromal cells and fibroblasts and a weak correlation with IL-6 as a SASP (specific senescent-associated secretory phenotype) were noted. Results of the multifactorial linear regression analysis showed that the blood plasma marker, VCAM-1, and the cell marker, 96-h increment of fibroblasts, were associated with PWV regardless of the patient's age.Conclusion    Stiffness of great arteries as measured by PWV significantly correlates with a number of plasma, tissue, and cellular markers for accumulation of senescent cells. This fact suggests PWV as a candidate for inclusion in the panel of parameters for evaluation and monitoring of the biological age during the senolytic therapy.

[PD-L1 expression in EBV-associated gastric carcinomas]. / Ekspressiya PD-L1 v EBV-assotsiirovannom rake zheludka.

OBJECTIVE: Assessment of the incidence of PD-L1 expression in EBV-associated gastric adenocarcinomas, as well as clarification of the clinical and morphological characteristics and median survival of patients with PD-L1-positive EBV-associated gastric cancer. MATERIAL AND METHODS: Samples of surgical material from 127 patients with stomach cancer were studied. Each sample was stained by in situ hybridization using primers for the Epstein-Barr virus-encoded small RNAs (EBER). Expression of PD-L1 was assessed immunohistochemically (PD-L1 SP263, PD-L1 SP142). The results obtained were compared with the main clinical and morphological characteristics of gastric cancer and median survival of patients. RESULTS: The detection rate of PD-L1 SP263 and PD-L1 SP142 in EBV-associated gastric adenocarcinoma in our sample was 100% and 76.9% respectively, thus, PD-L1 expression (SP263, SP142) is significantly more frequently detected in EBV-associated gastric carcinomas. It was found that patients with positive expression of PD-L1 in EBV-associated gastric carcinomas are younger (mean age 56.3 years for SP263 and 55.6 years for SP142), belonging to male gender. In addition, this group is dominated by proximal localization of tumors, ulcerative form of growth, tubular histological type, intermediate subtype according to P. Lauren. These characteristics do not depend on the antibody clone: positive expression of SP142 and SP 263 was detected in the same patients with a few exceptions. The overall median survival of patients with positive PD-L1 status SP263 in EBV-associated gastric carcinomas was 35 months, for patients with positive PD-L1 status SP142 - 25 months. Median survival of SP142 PD-L1 positive patients is higher than overall median survival of PD-L1 negative patients in EBV-associated gastric carcinomas. It was found that PD-L1 status in EBV-associated gastric cancer is not a significant prognostic factor. CONCLUSION: A single PD-L1 status does not significantly affect the prognosis in patients with gastric cancer, including those in the group of EBV-associated carcinomas, and can only be considered in conjunction with 'classic' clinical and morphological characteristics, primarily with the stage of the tumor process, since they determine the prognostic properties of the tumor.

[Study of gastric adenocarcinomas association with the Epstein-Barr virus-encoded small RNAs]. / Issledovanie assotsiatsii adenokartsinom zheludka s malymi virusnymi RNK virusa Epshteina­Barr.

OBJECTIVE: Assessment of the incidence of EBV-associated gastric adenocarcinomas in a sample of Russian patients, as well as clarification of the clinical and morphological characteristics and median survival of patients with EBV-associated gastric cancer. MATERIAL AND METHODS: We used samples of surgical material from 282 patients with a verified diagnosis of gastric cancer. Each sample was stained by in situ hybridization using primers for the Epstein-Barr virus-encoded small RNAs (EBER). The results obtained were compared with the main clinical and morphological characteristics of gastric cancer. RESULTS: The detection rate of EBV-associated gastric adenocarcinoma in our sample was 9.57%. EBER-positive tumors much more often (p=0.021) belong to the intermediate type according to the P. Lauren classification (66.67%) in comparison with EBER-negative tumors (38.82%). EBER-positive tumors significantly more often (p=0.035) belong to high-grade tumors - 75.00% in comparison with EBER-negative tumors (52.13%). The overall median survival of all patients with EBER-positive tumors (53.5 months) was higher compared to the overall median survival of all patients with EBER-negative tumors - 36.5 months (p=0.5379). The median survival of patients with EBER-positive stage III tumors (30.0 months) was also higher compared to that for patients with EBER-negative tumors - 20.0 months (p=0.5622). It was found that a single EBER status is not a significant prognostic factor (HR=1.0143; CI: 0.9897-1.0196). CONCLUSION: Separately taken EBER-status is not a significant independent prognostic factor and can be considered only in conjunction with the «classical¼ clinical and morphological characteristics, primarily with the stage of the tumor process, since it is they that determine the prognostic properties of the tumor.

Epstein-Barr Virus in the Development of Colorectal Cancer (Review).

The study of the influence of the Epstein-Barr virus (EBV) on the development of colorectal cancer is of current interest, particularly in light of the active discussion of the participation of this virus in the carcinogenesis of stomach cancer. In this review, aimed at a fundamental understanding of the processes associated with the impact of EBV on the human body, attention is paid to the issues of the life cycle of the virus, its phases (latent and lytic), as well as proteins that may be detected in each of the phases. The papers reporting on the role of EBV in the development of colorectal cancer have been analyzed. A summary table indicating the population under study, the number of samples, the method, and the result obtained is provided. Given that the primary cells affected by EBV are lymphocytes, it is logical to assume the involvement of this virus in the development of inflammatory bowel diseases. The review cites studies which confirm the presence of virus DNA in tissues in the inflammatory diseases of the colon, including microscopic and ulcerative colitis. To confirm the direct impact of EBV on the development of colorectal cancer, large studies with applying various methods for detecting the virus and the mandatory description of its localization are required. Besides, it is necessary to correlate these data with the clinical and morphological characteristics of EBV.

[Podoplanin`s expression in cancer-associated fibroblasts close to tumor budding of invasive edge]. / Ekspressiya podoplanina v opukholeassotsiirovannykh fibroblastakh vblizi opukholevykh pochkovanii invazivnogo kraya.

INTRODUCTION: Tumor budding was declared as independent prognostic factor for early cancer in 2016. Tumor-associated fibroblasts (CAFs) are one of the main components of tumor microenvironment. Plenty of different markers are used for detection of CAFs, including podoplanin (POD). OBJECTIVE: The aim of this study is to identify correlation between tumor budding, that indicates tumor invasive potential and is considered to be a negative prognostic factor, and CAFs near tumor buds using POD. MATERIAL AND METHODS: 43 cases of colon adenocarcinoma are included in the study. Double staining immunohistochemical technology with PCK and POD was used for detection of tumor budding and evaluation of POD expression near tumor buds. RESULTS: Significant correlations are revealed between tumor budding and depth of tumor invasion (p=0.023)/regional lymph node metastasis (p=0.068), but between POD expression and depth of tumor invasion (p=0.088) only a tendency of correlation is identified. These facts demonstrate critical prognostic value of tumor budding instead POD expression near tumor buds. It was found that intensity of POD expression near tumor buds is statistically analogous to POD expression in the invasive margin (p=0.0016). That means it is not necessary to evaluate POD expression exactly near tumor buds. For the first time stronger POD expression near mucin complexes is reported. That, probably, will allow to use mucin complexes as alternative prognostic factor instead tumor budding, as tumor buds are absent in mucinous adenocarcinoma.

[E-cadherin expression in tumor emboli in gastric cancer]. / Ekspressiya E-kadgerina v opukholevykh embolakh pri rake zheludka.

OBJECTIVE: To determine the level of E-cadherin expression in tumor emboli, to compare it with expression in a tumor, to determine the dependence of E-cadherin expression in tumor emboli on the clinical and morphological characteristics of gastric cancer. MATERIAL AND METHODS: We used samples of surgical material from 280 patients with a verified diagnosis of gastric cancer. E-cadherin expression was determined by immunohistochemical method. The results of the reactions were assessed semi-quantitatively and compared with the main clinical and morphological characteristics of gastric cancer (histological type according to the WHO classification 2019, histological type according to the classification of P. Lauren, clinical stage, depth of invasion (T), number of metastases in lymph nodes (N), presence or/absence of distant metastases (M), tumor localization in the stomach). RESULTS: Among 280 cases of cancer, emboli were detected only in 67 cases, used for further analysis. The rest of the samples were excluded from the analysis, since emboli did not get into the sections during the cutting of immunohistochemical preparations. The expression of E-cadherin in tumor emboli was significantly higher (p<0.001) than in tumor tissue. At the same time, no cases identified where the level of E-cadherin decreased in emboli compared to the tumor. A significant increase in the expression of E-cadherin in tumor emboli compared to the primary tumor was noted for all histological types according to WHO 2019, for intermediate and diffuse types according to the P. Lauren classification (p<0.001). Comparison of expression in emboli and tumors for neoplasms with different depths of invasion (T), different stages and different localizations did not reveal statistically significant differences. An increase in the expression of E-cadherin in emboli compared to tumors was characterized by a higher level of significance in the presence of metastases (N1, N2, N3a, N3b; p<0.001) than in the absence of metastases (N0; p=0.016). CONCLUSION: The study revealed a statistically significant increase in the expression of E-cadherin in tumor emboli compared to the primary tumor, which is evidence of its important role in maintaining the integrity of emboli and tumor dissemination.

[Persistence of Epstein-Barr virus antigens in gastric cancer: characteristic of inflammatory cellular reactions in tumor]. / Persistentsiya antigenov virusa Epshteina­Barr pri rake zheludka: kharakteristika vospalitel'nykh kletochnykh reaktsii v opukholi.

THE AIM OF THE STUDY: Is to establish the relationship between the persistence of viral antigens of the Epstein-Barr virus (EBV) and the cellular composition of the immune microenvironment of tumor tissue and the mucous membrane of peritumoral area in gastric cancer. MATERIAL AND METHODS: We used samples of surgical material from 55 patients with a verified diagnosis of gastric cancer. The expression of CD4, CD8, CD68, CD1a and LMP-1 was assessed. The results were assessed by the morphometric method. We selected three fields of view (magnification x200) in tumor tissue and in peritumoral areas separately and counted an absolute number of cells with positive staining with further calculation of the average number of cells and the median. RESULTS: LMP-1-negative tumors with LMP-1 expression in epithelium of peritumoral area were characterized by the highest density of CD4+ lymphocyte infiltration in the central part of the tumor; the highest density of CD8+ lymphocyte infiltration in the mucous membrane of peritumoral area (p=0.0190); the highest density of infiltration by macrophages in the mucous membrane of peritumoral area (p=0.2492); the highest density of infiltration by CD1a+ cells in the mucous membrane of peritumoral area (p=0.1503). The highest density of infiltration with CD1a+ cells was characteristic for LMP-1-positive and LMP-1-negative tumors (p=0.0813). The persistence of the LMP-1 viral antigen in the glandular epithelium of the peritumoral area in our sample does not have a statistically significant effect on the prognosis of the disease (RR=1.7718; p=0.0885) but there is a tendency towards a negative predictive value. CONCLUSION: High density of infiltration of glandular epithelium of peritumoral area with the expression of LMP-1 by CD4+ and CD8+ lymphocytes is most likely associated with the activation of the cellular immune response and may be one of the signs of the persistence of viral antigens. It was shown for the first time that the phenomenon of persistence of the LMP-1 viral antigen is characterized by a trend towards negative predictive value for patients with gastric cancer.

[Leptin and leptin receptor evaluation in atherosclerotic plaques in patients with type 2 diabetes mellitus].

BACKGROUND: Diabetes mellitus (DM) is a significant predictor of atherosclerosis, cardiovascular disease, and cardiovascular mortality. It is known that atherosclerosis occurs earlier in patients with diabetes, reducing the duration of their life. Leptin as well as other inflammatory markers can contribute to the progression of atherosclerosis in patients with DM, participate in the development of a local inflammatory reaction. AIM: Determine the cells immunophenotype of atherosclerotic plaques in patients with diabetes. MATERIALS AND METHODS: We analyzed 24 patients (20 men and 4 women), who underwent aortofemoral bypass, femoral-tibial bypass or carotid endarterectomy. During the operation, a fragment of the arterial wall with an atherosclerotic plaque was obtained for further immunohistochemical studies. Five histologic plaque characteristics (CD68+, -SMA, CD34, leptin and leptin receptor) were compared. RESULTS: No difference in the expression of CD68 (p=0.922), -SMA (p=0.192), CD34 (p=0.858), leptin receptor (p=0.741) and leptin (p=0.610) in atherosclerotic plaques were observed between patients with and without DM. The lack of significant differences between the two groups was possibly due to the small number of observations with DM. In particular, when assessing the expression of selected markers in atherosclerotic plaques, patients with DM showed significantly more leptin receptors than patients without DM (2160.716 and 1205.88 respectively); and also significantly less CD68+ (0.39 and 0.98 respectively) and -SMA+ (6.5 and 13.5 respectively). CONCLUSION: Based on the expression of CD68, -SMA, CD34, leptin receptor and leptin, no significant differences were observed in atherosclerotic plaque between patients with and without DM. At the same time, despite the limitations of the study (a small number of patients, moderate severity of DM, elderly patients in the DM group), we found a tendency in the increased number of leptin receptors and a decreased number of -SMA+, CD68+ in DM atherosclerotic plaques. Further study needed, taking into account the limitations of this work.

[Shear wave elastography guided targeted biopsy in the diagnosis of prostate cancer].

OBJECTIVE: to compare the effectiveness of targeted biopsy guided by the shear wave elastography (SWE) and systematic biopsy in the diagnosis of prostate cancer (PCa). MATERIAL AND METHODS: A total of 164 patients with suspected PCa were examined. Multiparametric TRUS, including SWE, was performed to all patients with the use of the Aixplorer ultrasound system (Supersonic Imagine, France), followed by TRUS guided 12-samples systematic prostate biopsy in combination with targeted biopsy from hypoechoic and/or stiff areas according to SWE data. Comparison of the results of histological examination and tissue stiffness measurements were carried out according to the specimens and patients. A total of 2 171 biopsy samples were analyzed (1 968 systematic and 203 targeted). After morphological evaluation all specimens were divided into groups of PCa+ (n=441) and PCa- (n=1 730), and patients to the group of PCa (n=74) and the control group (n=90). RESULTS: PCa was found in 17.3% of systematic biopsy specimens and in 76.9% of SWE targeted biopsy specimens (P<0.0001). The significant moderate positive correlations of Youngs modulus and Gleason scores (rS=0.51, P<0.0001), Youngs modulus and% specimen involvement (rS=0.59, P<0.0001) were founded in the group of PCa+ biopsy specimens. The percentage of PCa+ specimens was significantly higher with any types of targeted biopsy, than with systematic biopsy. With SWE targeted biopsy the percentage of PCa+ specimens was significantly higher than with B-mode guided targeted biopsy. Similar regularities were observed when comparing these types of targeted biopsy according to morphological prognostic ISUP groups and perineural invasion. Performing of targeted biopsy increased the morphological prognostic group in 5.4% of patients, additionally revealed perineural invasion in 2.7% of patients with PCa, and transferred additional 9.5% of patients from the group of clinically insignificant to the group of clinically significant PCa. CONCLUSION: SWE-guided targeted biopsy shows the significantly higher positive biopsy rate than conventional systematic biopsy. The use of SWE-guided targeted biopsy in addition to systematic biopsy can increase clinically significant PCa detection rate and improve the detection of perineural invasion.

[Changes in the classification of malignant colon epithelial neoplasms. (WHO, 2019, 5th edition)]. / Novoe v klassifikatsii zlokachestvennykh epitelial'nykh opukholei tolstoi kishki. (VOZ, 2019, 5-e izdanie).

There are not many changes compared to 2010 in WHO classification (2019) of colon adenocarcinomas. Cribriform comedo-type adenocarcinoma (ICD-O code: 8201/3), spindle cell carcinoma (8032/3), squamous cell carcinoma (8070/3) are excluded; carcinoma with a sarcomatoid component (8033/3), poorly cohesive carcinoma (8490/3) and adenoma-like adenocarcinoma (8262/3) were added. The important histological characteristics in the conclusion should indicate the presence of lymphatic invasion, intra- and extramural vascular invasion, perineural invasion, grading, «tumor budding¼ and the immune microenvironment. In the 5th edition of the classification a large section has been added regarding molecular diagnostics and molecular prognostic factors of colorectal cancer. Correspondence was found between two different classifications based on two different approaches: genomic (according to DNA analysis) and transcriptomic (according to RNA analysis). According to the genomic classification two large groups of colorectal cancer are distinguished: hypermutated and non-hypermutated cancers that correspond to molecular pathways with the development of microsatellite and chromosomal instabilities, respectively. The section of neuroendocrine tumors did not undergo significant changes. It is not recommended to use the term «carcinoid¼ to refer to a neuroendocrine tumor G1, that is, the term «carcinoid¼ is excluded.