[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.

Identification of Cancer-Associated Fibroblasts in Metastatic Lymph Nodes of Colorectal Carcinoma.

Cancer-associated fibroblasts (CAF) are a heterogeneous group of tumor microenvironment cells that are barely studied in metastatic lymph nodes. The presence of CAF in regional metastases of colorectal cancer was assessed by using SMA, PDGFRb, and POD markers; the obtained subpopulations were compared with the primary tumor. A total of 26 cases of colon adenocarcinoma with metastases to regional lymph nodes were studied. Duplex immunohistochemical detection (POD+SMA and PDGFRb+SMA) was carried out by the immunohistochemical method. In most cases, POD was absent in metastases (65.4%) and PDGFRb was present (88.5%). The POD and PDGFRb staining in the invasive edge of the tumor did not correlate with metastasis. Attention was drawn to the absence of POD and PDGFRb reactions in a blood vessel embolus, as well as to negative PDGFRb in metastasis in the presence of pronounced PDGFRb in the primary tumor in patients after neoadjuvant therapy.

[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.

[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.

[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.

[Claudin-3 expression in gastric cancer]. / Ékspressiia klaudina-3 v rake zheludka.

Claudins are a family of transmembrane proteins which are essential for the formation and maintenance of epithelial tight junctions. Altered expression of claudins may lead to structural and functional damage of tight junctions, which plays an important role in tumorigenesis and cancer progression. The expression of claudin-3 in gastric cancer is not yet well understood. AIM: To evaluate the expression of claudin-3 in gasric cancer and in adjacent normal mucosa and its association with clinical and pathological parameters. SUBJECT AND METHODS: Tissue specimens from a total of 69 patients with gastric cancer were obtained. Immunohistochemical reactions were performed using mouse polyclonal antibodies to claudin-3. RESULTS: The expression of claudin-3 in gastric cancer was significantly higher than in adjacent normal mucosa (p<0,05). The absence of claudin-3 was significantly associated with poor differentiation (p<0,05). An abnormal nuclear expression of claudin-3 was observed in 69.6% cases. A significant association was found between nuclear expression and the absence of membranous claudin-3 expression (p<0,05).

[A new one in the classification of benign colon epithelial tumors (WHO, 2019, 5th edition)]. / Novoe v klassifikatsii dobrokachestvennykh épitelial'nykh opukholei tolstoi kishki (VOZ, 2019, 5-e izdanie.

The 2019 WHO Classification of Benign Colon Epithelial Neoplasms includes serrated dysplasia, adenomatous polyps, and glandular intraepithelial neoplasia. Serrated dysplasia (ICD-O 8213/0 and 8213/2) is former serrated masses. There is an expected change in its terminology: it is proposed to use the term 'sessile serrated lesion' (SSL) instead of that 'sessile serrated polyp/adenoma' that causes a lot of discussion. The 2019 WHO Classification versus the 2010 WHO classification more clearly defines the TSA criteria: slit-like serration and high elongated cells with pronounced eosinophilic cytoplasm and an elongated pencillate nucleus. The traditional adenomas are renamed in the classification; the term 'adenomatous polyps' that still includes tubular, tubulovillous, and villous adenomas is adopted instead of the term 'adenomas'. The criteria for adenomas remain the same (by the area occupied by villous structures). The 5th edition introduces a separate large section devoted to inflammatory bowel disease-associated dysplasia that is defined as obvious epithelial neoplastic changes that are limited to the basement membrane. The diagnosis can only be used for specific lesions, such as Crohn's colitis and ulcerative colitis.

[Cancer-associated fibroblasts and their significance in tumor progression]. / Opukhol'-assotsiirovannye fibroblasty i ikh znachenie v progressii zlokachestvennykh novoobrazovanii.

Carcinogenesis and tumor progression are not caused not only by malignant epithelial cells, but also by the tumor stroma around cancer stem cells which performs regulatory, nutritional and 'framework' functions. It is represented by mesenchymal cells of various types predominantly by cancer-associated fibroblasts (CAF). αSMA, FAP-1, desmin, podoplanin, neuron-glial antigen 2 (NG2), PDGFR-α and -ß are used for CAF identification but there is no universal markers due to the plasticity of the cell population that underlies the subpopulation division CAF. CAF subpopulations are not described for many tumor types. Recently, evidence has accumulated that CAFs mediate many adverse processes in the tumor, including can support stromal inflammation and cause fibrosis. By forming a niche in cancer stem cells, CAFs mediate chemoresistance and the appearance of dormant metastases. The study of the role of CAF will allow not only to form a fundamentally new understanding of the mechanisms of carcinogenesis, but also to create new diagnostic and therapeutic targets for treating tumors.

[Expression of LMP-1 protein in tumor cells and glandular epithelium of the peritumoral tissue in gastric cancer]. / Ékspressiia belka LMP-1 v opukholevykh kletkakh i zhelezistom épitelii peritumoral'noi oblasti pri rake zheludka.

OBJECTIVE: To study the relationship of LMP-1 expression with the clinical and morphological characteristics of gastric cancer and to study LMP-1 expression in the glandular epithelium of the peritumoral tissue. MATERIAL AND METHODS: Samples of gastric cancer surgical material from 67 patients were included in this study. Primary mouse monoclonal antibodies to LMP-1 protein were used. LMP-1 expression was considered as positive if at least in one of the selected 10 fields of view (lens magn. ×40) ratio of the number of cells with LMP-1 expression to the total number of cells exceeded 10%. RESULTS: Nine cases of LMP-1 positive tumors, 32 cases of LMP-1 negative tumors and 26 cases of LMP-1-negative tumors with LMP-1-expression in the epithelium of the peritumoral tissue were detected. Last group was described for the first time; 4 of these were intestinal type tumors, 19 tumors were 'intermediate' type and 3 tumors were diffuse type, the prevalence of 'intermediate' type tumors was statistically significant. CONCLUSION: LMP-1-negative tumors with LMP-1-expression in the epithelium of the peritumoral tissue were identified and described for the first time. This group was predominantly represented by tumors of an 'intermediate' histological type of gastric cancer. EBV antigens may have any direct oncogenic effects, or play the role of the background or the concomitant processes. No significant relationship was found between the LMP-1 expression and depth of invasion (T), lymph nodes metastasis (N), distant metastasis (M), clinical stages. This fact can be explained by the high heterogeneity of molecular and genetic properties of gastric cancer.

[Epstein-Barr virus-associated gastric adenocarcinoma]. / Adenokartsinoma zheludka, assotsiirovannaia s virusom Épshteina-Barr.

EBV-associated gastric adenocarcinoma accounts for 10% of all gastric adenocarcinomas. The main known facts about the pathogenesis of EBV-associated gastric adenocarcinoma are presented. There are two main morphological types: gastric carcinoma with lymphoid stroma - GCLS (including lymphoepithelioma-like carcinoma; carcinoma with Crohn's disease-like lymphoid reaction; EBV-associated carcinoma with osteoclast-like giant cells) and conventional type adenocarcinoma. EBV-associated gastric adenocarcinomas predominantly express markers of gastric differentiation (MUC5AC, MUC6, CLDN-18) and a number of viral markers (EBER-1, EBNA-1 and BART mRNA). Three types of EBV latent cycle depending on the set of expressed viral transcripts are distinguished. It is believed that EBV-associated gastric adenocarcinoma is characterized by an intermediate position between latent cycles of types 1 and 2. The main method of virus identification is in situ hybridization with the detection of Epstein-Barr virus-encoded small RNAs (EBER-ISH).

[Coexpression of CD44 and Ki-67 in colon`s neoplast]. / Koékspressiia CD44 i Ki-67 v novoobrazovaniiakh tolstoi kishki.

AIM: the evaluation of Ki-67 and CD44 expression in the 'serrated' polyps of the colon and comparison them with adenocarcinomas and tubular and tubule-villous adenomas of the colon. MATERIAL AND METHODS: The study is including 49 'serrated' polyps, 34 tubular (AT) and tubulo-villous (ATV) adenomas and 32 adenocarcinomas of the colon. Antibodies CD44 and Ki-67 were used as immunohistochemical markers in this study. RESULTS: A statistically significant difference (p<0.01) was observed between traditional serrated adenomas (TSA) from hyperplastic polyps (HP) and sessile serrated adenomas (SSA) in the Ki-67 level and the localization of the Ki-67 and CD44 reaction: surface areas of the crypts (upper third) in TSA and base of crypts (lower third) in HP and SSA. There was no difference between HP and SSA (p>0.05), neither by marker localization, nor by their level. In all 'serrated' polyps of the colon, the Ki-67 reaction was nuclear; CD44 - membrane (except for 1 TSA). CONCLUSION: we are the first ones who suggested to evaluate not the overall level of reactions of CD44 and Ki-67, but particular level for each third part of crypts. The similarities of TSA, AT and ATV and between HP and SSA are shown as well as the principal statistical difference between these two groups. The cytoplasmic reaction of CD44 in adenocarcinomas and the membrane reaction of CD44 in 98% of the 'serrated' polyps of the colon are described. For the first time coexpression of CD44 and Ki-67 on particulate thirds of crypts in neoplasms of the colon is shown and the potential reasons for this phenomenon are discussed.

[Gastric adenocarcinoma arising in giant hyperplastic polyp]. / Adenokartsinoma v gigantskom giperplasticheskom polipe zheludka.

Gastric hyperplastic polyps are usually solitary, their development is supposed to be associated with excessive proliferation of foveolar cells. It is essential to differentiate hyperplastic polyps from other sporadic polyps (adenomatous and fundic gland polyps) and lesions, included in familial polyposis syndromes. The frequency of adenocarcinoma in large gastric hyperplastic polyps (more than 1-2 cm in size) is about 2,1%. This article includes case report of gastric adenocarcinoma arised in large hyperplastic polyp in a 56-year-old patient. On histological examination a well-differentiated adenocarcinoma without invasion in the peduncle was identified. Immunohistochemically cells of adenocarcinoma showed elevated expression of claudin-3, CDX2, p53 and Ki67 compared to hyperplastic glands and dysplastic areas of the polyp. Also focal expression of MUC2 was revealed in adenocarcinoma. Expression of MUC5AC, CD44 and cyclin D1 was less prominent in cancer areas compared to hyperplastic and dysplastic glands. Levels of expression of claudin-1, claudin-4 and ß-catenin were equal in adenocarcinoma and hyperplastic structures. Control endoscopic examination with following morphologic examination was performed three months after surgical operation. No signs of tumor growth were identified.