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Cytokeratins (CKs) are well studied as intermediate filaments of the cytoskeleton of epithelial cells, providing specific cell structure and morphology, in particular, apico-basal cell polarization. Meanwhile, a certain specificity of the association of CK with different types of epithelia is noted. CK heterogeneity in the glandular epithelium is particularly pronounced and is associated with anatomical localization. The relative specificity of CKs in epithelium of different localization is preserved to a great extent in carcinomas originating from this epithelium as well. Due to this fact the determination of CK spectrum in tumor cells is quite an effective tool for nosological diagnostics of carcinomas. however, the function of CKs is not limited to providing the cell structure. The presence and amount of CK changes during the most important processes in normal and tumor cells: movement/invasion, apoptosis, proliferation, epithelial-mesenchymal plasticity.A question arises: Is initiation of the above-listed processes happens first, and therefore CK changes are secondary and «passive», or in some processes CK changes can play a role of a trigger? Knowing the answer to this question is not only of fundamental importance, but is also important for finding ways to control the above processes by influencing the CKs.

lymphangitic carcinomatosis is characterized by the spread of cancer cells through pulmonary lymphatic vessels, which results in secondary interstitial inflammation. The diagnosis of lymphangitic carcinomatosis is challenging due to nonspecific clinical symptoms and radiological findings that similar to those of interstitial lung disease.The purpose of the study was to demonstrate difficulties in the diagnosis of lymphangitic carcinomatosis with a systemic dissemination from unknown primary site. Case presentation. We report on a case of lymphangitic carcinomatosis from cancer of unknown primary origin with systemic involvement of internal organs imitating pulmonary disease caused by coVid-19. patient K., 58 years old, was treated for 12 bed-days in therapy departments with the diagnosis of bilateral viral coVid-19 pneumonia. clinical, laboratory and instrumental data were nonspecific. despite treatment, heart failure and kidney disease progressed to terminal stages, leading to the death of the patient. Autopsy revealed systemic lymphangitic carcinomatosis from cancer of unknown primary origin with involvement of the lungs, heart, liver, pancreas, spleen, kidneys and adrenal glands. lymphangitic carcinomatosis mimicked interstitial lung disease in a novel coronavirus infection coVid-19. metastasis to the heart mimicked coronary disease, and metastases to the kidneys led to acute kidney failure, which along with acute respiratory and heart failure caused the death of the patient.Conclusion. lymphangitic carcinomatosis, which does not have specific clinical manifestations, is able to mimic interstitial lung diseases, including a new coronavirus infection. cancer of unknown primary and multiple visceral metastases in this case confirm the concept of the independence of different types of tumor progression.

Cardiac metastasis from endometrial cancer is a very rare finding. The article presents a case of death, demonstrating the aggressive clinical course of endometrial serous carcinoma. In this clinical example the disease was accompanied by generalized metastasizing through a lymphogenous route to unexpected distant organs (peribronchial lymph nodes, pleura, pericardium).

Purpose: to evaluate the crowding-induced morphological changes in invasive breast carcinoma and compare the data obtained with the parameters of the tumor progression. Material and Methods. The study group included 107 patients (mean age: 57.2 ± 11.2 years) who did not receive neoadjuvant chemotherapy. Breast cancer morphological and immunohistochemical images were studied. The histological type of breast cancer was determined according to WHO recommendations (The WHO Classification of Breast Tumors, 5th Edition, 2019). The study included only cases with invasive breast carcinoma of no specific type. Clinical parameters were assessed using the patients' medical history. Statistical analysis was carried out using the Statistica 10.0 program. A p-value of 0.05 or lower was considered statistically significant. Results. The phenomenon of crowding in breast cancer was shown to be associated with lymph node metastases, with intratumoral heterogeneity of particular importance. The phenomenon of crowding was morphologically confirmed in all cases (n=40) with lymph node metastases in solid tumors. In these solid tumor structures, a decrease in the expression level of the proliferative index Ki67 was observed. In tumor sites with the evidence of crowding phenomenon in solid structures with lymph node metastasis, positive expression of integrin β1 was less frequently observed. Conclusion. Te results obtained suggest that the mechanism that initiates the process of tumor cell invasion may be based on crowding and basal cell extrusion, while the patterns found are a manifestation of changes in cell properties with the acquisition of a higher potential for mobility and cell migration.

Background. Pancreatic cancer is characterized by pronounced invasive growth and a high tendency to lymphogenous and hematogenous metastasis. Molecular mechanisms underlying the epithelial-mesenchymal transition, in particular, changes in the expression of β1, β3 integrins and MMP2, contribute to the invasion and metastasis of pancreatic cancer. A phenotypic manifestation of invasive potential of pancreatic cancer may be the heterogeneity of the morphological structure of the parenchymal component of ductal adenocarcinoma.The aim of the study was to analyze the expression levels of β1 integrin, β3 integrin, MMP2 and the morphological heterogeneity in the tissue of pancreatic ductal adenocarcinoma, as well as to compare the data obtained with distant metastasis.Material and Methods. The study group included 84 patients with morphologically verifed pancreatic ductal adenocarcinoma (T1–4N0–2M0–1). The median age of the patients was 58.6 ± 9.1 years. All patients underwent surgery, during which an incisional biopsy of the primary tumor tissue was performed. Expression of integrin β1, integrin β3, and MMP2 markers was assessed by immunohistochemistry.Results. The positive expression of β3 integrin in glandular, trabecular, and solid structures was observed more frequently in patients with hematogenous metastases than in patients without distant metastases (87 vs 12 %, р=0.001; 100 vs 22 %, р=0.004; 100 vs 8 %, р=0.001, respectively). The positive expression of MMP2 in glandular and solid structures was also observed more often in patients with hematogenous metastases than in patients without distant metastases (87 vs 32 %, р=0.001 and 100 vs 27 %, р=0.001, respectively). The positive expression of integrin β1 in glandular, trabecular, solid structures and tumor cells was observed less frequently in patients with hematogenous metastases than in patients without distant metastases (27 vs 86 %, р=0.001; 25 vs 79 %, р=0.007; 0 vs 93 %, р=0.001 and 18 vs 60 %, respectively). The logistic regression model for predicting the risk of hematogenous metastasis of pancreatic ductal adenocarcinoma was developed: Y=(-6.71 + 30.9×X1 – 27.2×X2), where X1 – the presence or absence of β3 integrin expression in the cells of the glandular structures, X2 – the presence or absence of MMP2 in the cells of the glandular structures. The risk of developing hematogenous metastasis was determined by the formula: Р=еY/(1+еY). Model confdence interval: χ2 =34.0; p ˂ 0.001, sensitivity: 89 %, specifcity: 87 %.Conclusion. Expression of integrin β1, integrin β3, and MMP2 markers in various structures of the parenchymal component of pancreatic ductal adenocarcinoma is associated with distant metastasis. The localization of the expression of the studied markers in the glandular structures of tumor tissue is of particular importance. The presence of positive expression of integrin β3 and MMP2 in almost all types of tumor structures is associated with the highest frequency of distant dissemination.

Abstract Molecular subtype of breast cancer has a great clinical significance and used as one of the major criteria for therapeutic strategy. Recently, for anticancer therapy, the trend for oncologists is the predominant determination of biomarkers in the existing foci of the disease. In the case of adjuvant therapy prescribed for distant metastases prevention, CTCs could be a suitable object for investigation. CTCs as one of the factors responsible for tumor metastatic potential could be more convenient and informative for evaluation of hormone receptors, Ki-67 and HER2 expression, which are determine molecular subtype in breast cancer patient. In our study, we aimed to investigate the molecular subtype discordance between the primary tumor and CTCs in breast cancer patients. We established conversion of molecular subtype in most of the cases. Namely, conversion was detected in 90% of untreated patients and in 82% of breast cancer patients treated by neoadjuvant chemotherapy. At the same time, molecular subtype conversions in patients treated by neoadjuvant chemotherapy were more diverse. Molecular subtype conversions resulted more often in the unfavorable variants in circulating tumor cells. We stratified all patients according to the adequacy of treatment against converted CTCs molecular subtype. Our study revealed that good response to neoadjuvant chemotherapy observed in case of adequate therapy, namely, when chemotherapy scheme was sufficient against CTCs. It turned out that patients with inadequate therapy were characterized by decreased simulated 5-year metastasis-free survival compared to patients who received appropriate therapy. Thus, detection of molecular subtype conversion in circulating tumor cells could be a perspective tool for optimization of antitumor therapy.

Purpose of the study: to assess the relationship between atypical/hybrid forms of EpCAM+CD45+ cells in ascitic fluid of ovarian cancer patients and the levels of cancer markers, such as CA125 and HE4, and the tumor grade. Material and methods. The study included 48 patients with newly diagnosed ovarian cancer (42 patients with stage Ic–IV ovarian cancer and 6 patients with borderline ovarian tumors (Bots). The age of the patients ranged from 36 to 76 years. the study material included ascitic fluid and blood samples. the presence of atypical/hybrid forms of EpCAM+CD45+ cells in ascitic fluid was identified by laser multicolor flow cytometry. The levels of CA125 and HE4 markers were measured by ELISA. Results. The number of EpCAM+CD45+ cells in ascitic fluid of patients with serous ovarian carcinoma was 1.02 (0.30; 2.68) cells/µl (0.55 (0.03; 4.51) cells/µl in patients with low-grade serous carcinoma (LGSC) and 1.36 (0.41; 2.68) cells/µl in patients with high-grade serous carcinoma (HGSC). The number of EpCAM+CD45+ cells in ascitic fluid of serous ovarian carcinoma was shown to have a strong correlation with СА125 and HE4 levels in blood serum (R=0.60; р

The aim of the study: to examine the relationship between the morphological diversity of non-small cell lung cancer and the frequency of lymph node metastasis in groups of patients with different epithelial conditions in the bronchi adjacent to the tumor. Material and methods. Surgical specimens from 90 patients with non-small cell lung cancer, who were treated in the Thoracoabdominal Department Of The Research Institute Of Oncology Of The Tomsk National Research Medical Center in the period from 2009 to 2017 were studied. The histological type of cancer was determined according to the who classification (2020). Lepidic, acinar, papillary, micropapillary, solid and solitary tumor cells were isolated in the parenchymal component of adenocarcinoma. In the parenchymal component of squamous cell carcinoma, 5 types of structures were distinguished: with keratinization, consisting of atypical cells of the prickly type without keratinization, consisting of atypical cells of the basaloid type, built of atypical cells with pronounced polymorphism, single tumor cells. Results. In patients with isolated basal cell hyperplasia, acinar (37 %), papillary (29 %) and solid (27 %) patterns were found less frequently in cases with metastatic regional lymph nodes compared to those without metastatic lymph nodes (63 %; p=0.05; 71 %; p=0.05; 73 %; p=0.01, respectively). In patients with isolated basal cell hyperplasia of the bronchial epithelium, in cases with the presence of lymph node metastasis in the parenchymal component of squamous cell carcinoma, structures 1 (with keratinization) (17 %), 2 (spiky pattern) (33 %) and 4 (polymorphic pattern) (29 %) were less frequently detected compared to those without metastases in regional lymph nodes (83 %; p=0.01; 67 %; p=0.02 and 71 %; p=0.01, respectively). In patients with a combination of basal cell hyperplasia and squamous metaplasia, a spiny pattern (65 %), a basaloid pattern (100 %), a polymorphic pattern (82 %) and single tumor cells (89 %) were more frequently detected in cases with metastatic lymph nodes than in cases without metastatic lymph nodes (35 %; р=0.04; 0 %; р=0.01; 18 %; р=0.01; 11 %; р=0.01, respectively). Conclusion. The data obtained clarify the available information on the significance of the morphological heterogeneity of the tumor for predicting the course of adenocarcinoma and squamous cell carcinoma of the lung.

The treatment of colon cancer with a mesenchymal-like phenotype poses a great challenge. Purpose of the study: to research expression of FRMD6, ZEB1, HTR2B, CDX2 in the primary tumor tissue with relation of the clinical and pathological features of colon cancer. Material and methods. a combined analysis of the expression of FRMD6, ZEB1, HTR2B, CDX2 with pathological criteria was performed in 100 patients with T1–4bN0–2bM0 colon cancer. Results of the study show that tumors with mesenchymal signs are characterized by a large size of the primary tumor, a high grade of differentiation, regional metastases, and eventually advanced stage of the disease. The frequency and expression levels of FRMD6, ZEB1 and HTR2B are depended of grade of adenocarcinoma. in cases with positive expression and a high percentage of expression of these proteins in the cancer cells, the degree of tumor morphological anaplasia increases. Conclusion. The study made it possible to reveal the relationship of IHC markers (FRMD6, ZEB1, HTR2B, CDX2) with tumor characteristics that determine the outcome. The studied markers may have prognostic and predictive value in treatment approaches of colon cancer.

The purpose of the study was to generalize information regarding the molecular and biological mechanisms involved in the resistance to endocrine therapy with aromatase inhibitors in patients with luminal breast cancer. Material and Methods. The literature search was conducted using Medline, Cochrane Library, Elibrary and PubMed databases. Results. The review highlights the results of international studies on molecular and biological characteristics of breast tumors and their relationship with the effectiveness of hormone therapy. Particular attention was paid to the description of modern studies on ROR1 and BMI-1 proteins and their contribution to the development of tumor resistance to treatment. Conclusion. The analysis of the world literature confrms the relevance of studying the molecular and genetic characteristics of tumor tissue in patients with luminal breast cancer. The data obtained were compared to the clinical course and response to hormone therapy in order to standardize them for implementation in everyday practice as the “gold standard of diagnosis”.

Abstract. Breast cancer is one of the most commonly diagnosed cancers worldwide. According to the World Health Organization, the incidence of breast cancer was 2.26 million in 2020, overtaking the incidence of lung cancer. In Russian Federation, the increase in new cases of breast cancer over the ten years from 2005 to 2015 was 31.76 %. Microscopic calcium deposits within breast tissue, microcalcifications, can be early signs of breast cancer. Being a significant diagnostic finding, microcalcifications allow the assessment of the extent of the disease. A detailed understanding of the morphogenesis of microcalcifications can improve knowledge about early stages of breast cancer, but there is no studies that would combine the results of the latest basic scientific research and current knowledge about their clinical significance.The aim of the study was to analyze and summarize the available data on the prognostic value of microcalcifications in patients with breast cancer.Material and Methods. A search was carried out for available literary sources published in the Medline, Elibrary, etc. databases for the period since 2015. A total of 250 sources devoted to the analysis of the morphogenesis of microcalcifications and their diagnostic value were found. Of them, 37 were included in this review.

Ovarian cancer is one of the most malignant and aggressive tumors of the female reproductive system. Late diagnosis is one of the most significant problems: more than two-thirds of cases are detected only at stage III–IV. Ovarian cancer is characterized by a unique metastatic process. Implantation is the earliest and most common way of metastasis. It is often accompanied by fluid accumulation in the abdominal cavity, known as ascites. We report a case of low-grade serous ovarian carcinoma with a large heterogeneity of tumor cells in the ascitic fluid detected using multicolor flow cytometry. We demonstrated the advantages and benefits of this method in the diagnosis of ovarian cancer. Multicolor flow cytometry opens new horizons for liquid biopsy in oncology.

Introduction. Ability of circulating tumor cells (CTC) initiate metastases in distant sites is associated primarily with their resistance to apoptosis which allows them to retain viability in the blood. Knowledge of phenotypical signs associated with this ability would allow to predict the risk of metastases and optimize adjuvant therapy.Aim. To examine signs of apoptosis in CTC populations with various phenotypical characteristics.Materials and methods. The study included 58 patients with invasive breast carcinoma of unspecified type, stages T1–4N0–3M0. Cell concentrates extracted from patients’ whole blood were stained with an antibody cocktail against CK7 / 8, CD45, EpCAM, CD44, CD24, CD133, ALDH, N-cadherin which allowed to identify CTC with signs of stemness and epithelial-mesenchymal transition. Annexin V and 7‑amino-actinomycin D staining was used for evaluation of apoptosis stage in CTC populations.Results. Circulating tumor cells are characterized by heterogeneity in respect to signs of stemness and epithelial-mesenchymal transition and presence of early and late signs of apoptosis and necrosis. CTC phenotypes including co-expression of epithelial marker CK7 / 8 and stemness marker CD133 (but not CD44) are characterized by absence of signs of apoptosis. Co-expression of CK7 / 8 and CD133 in CTC with stemness markers CD44+ / C D24– is associated with development of early but not late signs of apoptosis and necrosis. Circulating tumor cells without co-expression of CK7 / 8 and CD133 could have both early and late signs of apoptosis and necrosis. Circulating tumor cells phenotypes with signs of early apoptosis expressing CD133 remain in blood after non-adjuvant chemotherapy opposed to CTC without CD133 expression.Conclusion. There are CTC phenotypical signs associated with stemness and epithelial-mesenchymal transition and linked to apoptosis resistance or sensitivity.

Background. Pseudosarcomas of soft tissues can cause diagnostic and treatment challenges. On the one hand, it is difficult to make a nosological diagnosis based on a biopsy specimen of a tumor; on the other hand, it is difficult to determine the most appropriate treatment strategy based on a histological pattern.The purpose of the study was to analyze available literature data and systematize the histological characteristics of the chondroid lipoma and pseudosarcoma.Case description. We present the case of chondroid lipoma in a 57-year-old female patient with atypical clinical symptoms. This case shows the difficulties of differential diagnosis of soft tissue sarcomas. Using a clinical example of chondroid lipoma, a rare soft tissue tumor, and an analysis of literature data, the authors showed the importance of a detailed study of the obtained material, a qualified description of the morphological picture, in those cases when the diagnostic conclusion cannot be unambiguous about the malignancy of the tumor process. Additional biopsy is not always possible to clarify the histotype of the tumor. The presented observation shows the difficulties of differential diagnosis of soft tissue sarcomas. Minimally invasive biopsy provides no a full appreciation of histological structure; therefore, if there is a suspicion for chondroid lipoma, it is necessary to perform total surgical biopsy followed by a morphological study using the immunohistochemical method.

Background. Peritoneal carcinomatosis (PC) is one of the most unfavorable factors of ovarian cancer progression. It is often accompanied by accumulation of fluid in the abdominal cavity, which is called ascites. However, prognostic factors associated with malignant ascites are not well understood.The aim of this study was to evaluate dissimilar populations of EpCAM-positive cells in ascitic fluid and their relationship with the presence of invasive peritoneal implants and the prevalence of carcinomatosis on the Predictive Index Value (PIV) scale in ovarian cancer patients.Materials and methods. The prospective study included 22 patients aged 36–76 years with newly diagnosed FIGO stage Ic–IV ovarian cancer, who were admitted for treatment to Cancer Research Institute of Tomsk NRMC. The study material included EDTA-stabilized ascitic fluid sampled during laparoscopy. Various populations of ascites tumor cells were identified by laser multicolor flow cytometry. The degree of carcinomatosis was determined according to the PIV scale.Results. The study identified twelve populations of EpCAM-positive cells in the ascitic fluid of ovarian cancer patients. Epcam+CD45-CD44-CD24+CD133-Ncadherin+ cells (r = 0.58; p = 0.004) and atypical (hybrid) EpCam+CD45+CD44+CD24+/-CD133+/-Ncadherin+/- cells (r = = 0.51; р = 0.01) had a positive correlation with the PIV index.Conclusion. The obtained results show a high degree of heterogeneity of tumor cells in the ascitic fluid of ovarian cancer patients. Identified atypical (hybrid) forms of EpCam-positive cells are of great interest for cell biology and require further investigation.

Purpose of the study: to review the available data on the heterogeneity of colon cancer and to assess the prognostic significance of colon cancer subtypes.Material and Methods. Medline, PubMed, Cochrane library, elibrary databases were used to identify studies that characterized the current view on the problem of choosing the optimal postoperative treatment for colon cancer.Results. the review showed the results of international studies of colon cancer subtypes based on complex multomics characteristics. Particular attention was paid to the description of modern studies on the search for prognostic markers for colon cancer. The relevance of the study of immunohistochemical markers was confirmed by the analysis of the world literature. the outcomes will make it possible to classify colon cancer into molecular subtypes in real clinical practice and, as a consequence, significantly improve the effectiveness of adjuvant therapy.

The purpose of the study was to analyze and summarize data regarding a significance of PD -L1 expression in various molecular subtypes of colorectal cancer.Material and Methods. A systemic literature search was conducted in the electronic databases Medline, Cochrane Library, Elibrary, PubMed. Of identified and reviewed 201 full-text articles, we included data from 47 studies.Results. The literature review described the features of the molecular genetic classification of colorectal cancer and revealed the key characteristics of each of the molecular subtypes of this disease. Much attention was paid to the molecular mechanisms of anti-PD -1/PD -L1 therapy. The main problems associated with the standardization of methods for pathomorphological assessment of the expression of this marker and the difficulties of its interpretation in colorectal carcinomas were outlined.Conclusion. Analysis of the literature revealed problems associated with the assessment of PD -L1 expression in colorectal cancer, in particular, with the lack of generally accepted methods for interpreting research results and standardizing methods for pathomorphological diagnosis of malignant tumors of this localization. Further studies are needed for introducing the molecular genetic classification of colorectal carcinomas into a wide clinical practice and personalizing the approach to therapy of this disease.

Background. The identification of predictive molecular markers of luminal breast cancer will help to assess the risk of developing distant metastases and determine a personalized approach to predicting the outcome of the disease during hormone therapy.The aim of the study was to investigate the relationship between the transcription factors GATA3, FOXA1, and ELF5 in the tumor and the occurrence of distant metastases in patients with luminal subtype of breast cancer during adjuvant hormone therapy.Materials and methods. The study included 101 patients with breast cancer (aged from 30 years to 81 years, average age (54.8 ± 10.3) years), with stages T1–4N1–3M0 of the disease. The follow-up period was at least 5 years. The inclusion criteria for the study were luminal molecular genetic subtype of the tumor and lack of preoperative treatment. The exclusion criterion was stage IV disease. The study of transcription factors was carried out by the immunohistochemical method using polyclonal antibodies to GATA3, FOXA1, and ELF5, manufactured by Flarebio (Austria).Results. Low expression of FOXA1 and ELF5 in the tumor was associated with the development of distant metastases (p = 0.000015 and p = 0.000002, respectively). In addition, it was found that high incidence of hematogenous metastases was associated with heterogeneous expression of FOXA1 (χ2 = 6.42; p = 0.01) and ELF5 (χ2 = 14.46; p = 0.0001) in the tumor. No similar differences were found in the study of GATA3 expression.Conclusion. The level of expression of transcription factors FOXA1 and ELF5 and their distribution in the primary tumor can be considered as potential molecular markers in assessing the risk of hematogenous metastasis in patients with luminal breast cancer.

Hormone-receptor positive breast cancer is the most common molecular subtype and represents 60–75 % of all breast cancers (BC). The presence of specific molecular targets such as the estrogen/progesterone receptor determines the use of hormone therapy for patients with this subtype. Tamoxifen, a selective estrogen receptor modulator, remains the first adjuvant treatment choice for the hormone-receptor positive BC patients. However, tamoxifen resistance is the major limitation of its efficacy. In this regard, the study of drug resistance mechanisms as well as search for biological prognostic markers of tamoxifen efficacy is very important. Cyclin D1 is a representative of the regulatory protein family, which plays a central role in the cell cycle regulation. The data on the association between cyclin D1 and estrogen-dependent signaling as well as the characteristics of CCND1 gene and its most studied polymorphic loci, were presented. The prognostic significance of cyclin D1 in hormone-receptor positive BC receptor-positive breast cancer was described. The experimental and clinical studies data on the association between the cyclin D1 expression level and tamoxifen efficacy are analyzed. Current approaches to overcoming hormone resistance based on cyclin D1 studies were considered.

Purpose of the study: to review available data on the role and significance of GATA3, FOXA1 and ELF5 transcription factors in the pathogenesis, progression and therapy resistance of breast cancer.Material and Methods. The Medline and PubMed databases were used to identify all studies that evaluated the structure, functional parameters and participation of the studied transcription factors in the pathogenesis of breast cancer. More than 180 publications were analyzed, of which 76 were included into the review.Results. The review shows that molecular genetic studies in relation to transcription factors and subsequent comparison of the obtained results with various clinical and morphological characteristics of breast cancer are of great importance. The review also demonstrates the inconsistency of the available data regarding clinical significance in assessing the prognosis of the disease and the sensitivity of the tumor to hormone therapy.Conclusion. The study of the expression parameters of GATA3, FOXA1, and ELF5 transcription factors, as well as their relationship with tumor progression mechanisms will increase the reliability of immunomorphological studies, most likely suggesting the efficiency of hormone therapy. Therefore, the results of this study can help to plan adequate treatment tactics and predict outcomes in patients with breast cancer.

Lafora disease is a hereditary, autosomal recessive progressive myoclonus epilepsy caused by mutations in the EPM2A (laforin) and EPM2B (malin) genes, with no substantial genotype-phenotype differences between the two. Clinical manifestations of the disease are determined by the accumulation of specific cytoplasmic “amyloid inclusions” consisting of polyglycosans (an abnormally branched glycogen molecule). Polyglycosans, or Lafora bodies, are typically found in the brain, hepatocytes of the liver, skeletal and cardiac muscles, in the ducts of sweat glands, and in the skin. The diagnosis is made following visual, generalized tonic-clonic and myoclonic seizures, progressing dementia, cerebellar ataxia, detection of specific Lafora bodies during sweat gland biopsy and data of genetic testing.The article describes a clinical case of Lafora disease in a patient with disease onset at 11 years old caused by the mutation in the EPM2A (laforine) gene with focal sensory visual seizures with subsequent generalized tonic-clonic seizures, progressive motor impairments in the form of ataxia and gait abnormality as well as behavioral and cognitive disorders. The presented clinical case demonstrates the need for additional research, such as biopsy and genetic testing, for diagnosing diseases proceeding with resistant epileptic seizures and progressive motor and cognitive impairments.

Currently the impact of autophagy on carcinogenesis remains understudied. On the one hand, autophagy acts as a tumor suppressor, as it activates degradation of oncoproteins, toxic proteins, and damaged cell organelles, that may be aggressive and lead to DNA damage. On the other hand, autophagy may promote tumor cell survival under hypoxia and in the presence of reactive oxygen species, which occurs primarily due to blocking of apoptosis mechanisms, raising the chances for maintaining tumor clone dynamics. Autophagy regulation is a complicated and multi-stage process. The main regulator here is a signaling pathway that activates serine/threonine protein kinase m-TOR (the mammalian target of rapamycin). Data on the impact of autophagic proteins ATG5, LC3A, LC3B, and Beclin-1 on malignant cell survival as well as on tumor growth and progression have been reported in literature. However, studies aimed at seeking possible relationships between autophagy and pathogenetic mechanisms of carcinogenesis are of great interest.The aim of the study is to investigate a relationship between the expression parameters of autophagy regulatory proteins m-TOR and Beclin-1 and the features of lymphogenic metastasis in colorectal cancer.Materials and methods. The study included 105 patients with T1-4N0-3M0 colorectal cancer treated in the Thoracic and Abdominal Department of Cancer Research Institute of Tomsk Research Medical Center from 2012 to 2015. The average age of patients was 59.7±4.3 years. Morphological verification of the diagnosis was performed on the biopsy samples of primary tumor tissue. Staging of colorectal cancer was determined according to the TNM classification of malignant tumors (2002).Results. Analysis of the frequency of lymphogenic metastasis depending on the presence or absence of m-Tor and Beclin-1 expression in tumor cell cytoplasm revealed a statistically significant link between these variables.Conclusion. The obtained findings clearly exhibit that deceleration or loss of autophagic activity in the tumor is accompanied by implementation of lymphogenic dissemination, which is a predictor of an unfavorable outcome of the disease.

The purpose of the study was a review of available data on the role of autophagy and angiogenesis in the development, progression and prognosis of colorectal cancer. Material and methods. Databases searched were Medline, Cochrane Library and Elibrary. Of 340 studies, 48 were used to write a systematic review. Results. To date, there is a variety of prognostic markers used in the study of pathogenesis, diagnosis and treatment of colorectal cancer. The review describes the molecular mechanisms of the participation of various proteins of autophagy and angiogenesis in the pathogenesis and progression of colorectal cancer, and the potential importance of their use in clinical practice is presented. Conclusion. Many of the existing markers can be used not only in assessing the prognosis, but also sensitivity to chemotherapy. However, the contradictory results of studies with respect to certain proteins require further study, validation, and subsequent introduction into practice.

Currently, the study of the markers of cell differentiation, proliferative regulators, and molecules involved in the development of drug resistance mechanisms in breast cancer is extremely important. The transcription factor GATA3 plays an essential role in the differentiation and proliferative activity of luminal breast cancer cells, being a tumor suppressor. The GATA3 positive expression is most frequently observed in invasive carcinoma of no special type. High expression of GATA3 is associated with low-grade ER-positive cancer with a favorable prognosis. Low GATA3 expression is observed in patients with high-grade and hormone receptor-negative cancer. The study of GATA3 expression is necessary for understanding the development of drug resistance mechanisms and developing approaches to overcome them as well as for determining the response to hormone therapy. Aim. The present study was undertaken to study the expression characteristics of the transcription factor GATA3 in patients with luminal breast cancer and to evaluate their relationship with the parameters of lymphogenous metastasis. Material and methods. The study included 64 patients with stage T1–4N1–3M0 invasive breast cancer. The primary tumor tissue and all removed lymph nodes were morphologically examined. The diagnosis was established according to the WHO criteria (2012). Results. Low GATA3 expression was associated with a high risk of lymph node metastases, while high GATA3 expression was associated with the absence of lymph node metastases. Heterogeneous GATA3 expression was associated with high risk of lymph node metastasis, and as a consequence, with poor prognosis. Conclusion. The relationship between the expression of GATA3 protein and lymphogenic metastasis in patients with luminal breast cancer was found.

Pancreatic cancer is one of the most unfavorable malignancies. Approximately 20 % of patients with pancreatic cancer have resectable disease at the time of diagnosis, however the prognosis of the disease in these patients remains poor, and the overall 5-year survival rate is only 5 %. The evaluation of morphological features, as well as features of the expression of markers that determine the invasive potential of such neoplasms, can serve in the future as a fundamental basis in solving problems concerning prognostic factors in pancreatic cancer. The purpose of the study was to evaluate morphological and immunohistochemical features of pancreatic ductal adenocarcinoma. Material and methods. The study included 84 patients with stage T1–4N0–2M0–1 pancreatic cancer. The age range was from 37 to 83 years. Surgery was the main treatment option. Morphological examination of surgical specimens showed that the tumor histotype corresponded to pancreatic ductal adenocarcinoma. The preparation of histological specimens and immunohistochemical staining were carried out according to standard procedures. Results and conclusion. This study allowed us to determine the features of tumor morphology, as well as the features of expression of markers associated with more pronounced invasive properties of the tumor. The results of this study may be of interest in terms of their further comparison with the parameters of various forms of progression in pancreatic cancer.

Angiogenesis (neoangiogenesis) characterized by the formation of new blood vessels from pre-existing vessels is the main condition for the intensive growth of the primary tumor. This process is characterized by a sequence of events beginning with vasodilation, separation of pericytes from the vascular wall with subsequent proliferation of endotheliocytes and formation of vascular glomeruli surrounded by stromal cells. Evaluation of the density of microvessels, as well as «vascular kidneys» (clusters of endotheliocytes) is the most widely used method for quantifying intracellular angiogenesis. The purpose of the study was to analyze the expression characteristics of markers of neoangiogenesis (CD34 and VEGFR) in tumor tissue and to evaluate their relationship with the parameters of lymphogenous metastasis in colorectal cancer. Material and methods. Surgical specimens from 130 patients with ypT1–4N0–2M0 stage of rectal cancer, who were treated at the Thoracic and Abdominal Department of Tomsk Cancer Research Institute, were analyzed. The standard techniques for histological and immunohistochemical examinations were used. Diagnose was made according to WHO classification (2010). The study included only cases with rectal adenocarcinoma. Results. When studying the density of microvessels and «vascular budding» in a tumor tissue using an antibody to CD34, it turned out that the density of microvessels in the submucosal layer of the rectum was higher in cases with the presence of lymphogenous metastases than in cases without lymphogenous metastasis. The microvessel density determined by the antibody to VEGFR in the mucosa, submucosal and muscle layers, as well as in the serosa of the rectum did not differ between groups with the presence or absence of lymphogenous metastases. The density of «vascular kidneys» in all layers of the rectum wall was not associated with lymphogenous metastasis. Conclusion. The study showed that the expression of molecular-biological markers of neoangiogenesis in tumor tissue of patients with rectal adenocarcinoma was associated with the parameters of lymphogenous metastasis.

When examining prostate cancer, a great attention is currently paid to the study of specific molecular characteristics of the tumor. It has been found that TMPRSS2-ERG is the most common fusion gene in prostate cancer. The fusion between TMPRSS2 and ERG/ ETV1 transcription factor genes participating in the processes of growth, differentiation and transformation of cells has been described in prostate cancer. During carcinogenesis, TMPRSS2 allele loses its promoter, and one of the ERG alleles gains that promoter leading to its overexpression in these tumor cells. Prostate and breast cancer overexpressed 1 (PBOV1) promotes proliferation of tumor cells by inhibiting the cell cycle and increasing the level of cyclin D1. It has been shown that the PBOV1 gene expression is regulated by androgens through FOXA-1 and FOXA-2 transcription factors and participates in the organogenesis in the embryo, as well as it controls the division of stem cells in adults, and plays a role in the development of certain types of malignant tumors. The purpose of the study was to analyze the expression of ERG and PBOV1 genes in acinar prostatic adenocarcinoma and evaluate their relationship with morphological characteristics and lymph node metastases. Material and methods. Surgical specimens from 85 patients with stage T1–3N0–3M0 prostate cancer were morphologically studied using standard techniques. All patients underwent radical prostatectomy. Histological type of the tumor was evaluated according to the 2016 WHO classification of tumors, and the tumor grade was assessed using the Gleason scoring system. Immunohistochemical examination was performed according to the standard technique. The expression of ERG (Clone, EP 111) and PBOV1 (Polyclonal) was assessed using histological scoring system. Proliferative activity was analyzed using Ki67 nuclear staining (Clone, SP6). Data analysis was performed using Statistica 10.0. Results. The high expression level of ERG and PBOV1 proteins was associated with tumor grading (Gleason score > 6) and lymph node metastasis. Inflammatory cell infiltration of the tumor was not associated with the frequency of lymph node dissemination. However, the presence of stromal retraction in acinar tumors was found to be associated with more frequent involvement of regional lymph nodes. The level of PBOV1 expression in tumor cells correlated with proliferative activity and associated with tumor invasion into seminal vesicles. Conclusion. The study showed the relationship between ERG /PBOV1 proteins and morphological characteristics of acinar adenocarcinoma of the prostate as well as the frequency of lymph node metastasis, thus indicating prognostic significance of these markers.

Introduction. The crosstalk between the estrogen and growth factor receptors signaling may play an important role in the resistance to endocrine therapy. The aim of the study was to examine the relationship between the protein and receptor gene expression of transforming growth factor β type I (TGF-βRI) and its polymorphism with progression of luminal breast cancer patients treated by adjuvant tamoxifen. Material and methods. The study included 105 patients with luminal breast cancer (T1-3N0–3M0), who had received adjuvant tamoxifen at a dose of 20 mg/day for at least 5 years. Patients who developed distant metastasis or recurrence after tamoxifen therapy were defined as tamoxifen resistance (TR) group, while distant metastasis-free patients were analyzed as tamoxifen sensitive (TS) group. TGF-βRI expression level was evaluated using immunohistochemistry. TGF-BRI gene expression and genotypes for rs334354 SNP were detected by a Real-time PCR. Results. We found high TGF-βRI gene expression in patients with luminal A subtype compared with luminal B breast cancer (p=0.050). The Int7G24AA and Int7G24A mutant carriers were more prevalent in luminal A breast cancer patients (p=0.019 and p=0.007, respectively). TGF-βRI protein expression level was significantly higher in the tamoxifen sensitive group compared to tamoxifen resistance breast cancer patients regardless of molecular subtypes (p=0.043). There was a trend for a tamoxifen sensitivity among luminal B breast cancer patients with a high TGF-βRI protein expression (p=0.090). Conclusion. TGF-βRI protein expression level can be a potential molecular marker of tamoxifen resistance in luminal breast cancer patients.

The processes of vital activity of cancer cells mainly depend on the production of growth factors and their receptors. The epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptor tyrosine kinases. Normally, binding of EGFR ligands and transforming growth factor alpha (TGFα) induces receptor activation, which triggers erk and PI3K signaling pathways that control cell proliferation, migration, invasion and many other processes. A number of studies have shown that a high percentage of EGFR expression is observed in 25–82 % of cases with rectal cancer. Thus, the expression and mutation of the EGFR gene is associated with various variants of tumor progression and an unfavorable prognosis for malignant tumors of various localizations. The purpose of the study was to investigate the EGFR expression in cancer tissue and evaluate the relationship between EGFR expression and parameters of lymphogenous metastasis in patients with rectal cancer. Material And Methods. Surgical specimens of 149 patients with stage T1–4N0–2M0, rectal adenocarcinoma, who were treated at the Cancer Research Institute of Tomsk National Research Medical Center, were studied using histological and immunohistochemical analyses. Positive EGFR expression was found in 88 (59.1 %) patients. Diagnosis was made according to WHO classification (2010). Results. When studying the EGFR expression in tumor cells on different depth of invasion, it was found that the positive expression of this marker was observed in cases with and without lymph node metastases. The analysis of the EGFR expression in various structures of the parenchymatous component of the tumor located in different layers of the intestinal wall showed that in the solid structures of the mucosa, the positive expression of EGFR was detected more often in cases without lymph node metastases. In patients with lymph node metastases, the percentage of the EGFR expression was lower. A similar pattern was observed in discrete groups of tumor cells. Conclusion. The study showed the presence of heterogeneity of the expression characteristics of the epidermal growth factor in various tumor structures located at different depths of infestation. The relationship between the parameters of lymphogenous metastasis and the positive EGFR expression indicates the prognostic significance of this marker.

Progressive subcortical vascular leukoencephalopathy caused by chronic hypertension was singled out as a separate disease by Alois Alzheimer and named “Binswanger’s Disease”(BD). Before the introduction of neuroimaging techniques in clinical practice BD was considered as a rare disease and in most cases it was diagnosed during autopsy. More than 80% of BD’s debuts occur on the sixth or seventh decade of life and are characterized by a mild but inexorably progressive course with episodes of exacerbation. At the last stage of the disease, clinical picture is presented by dementia, disorders of the self-service and the pelvic organs functions. The article presents a 42 years-old patient with the terminal stage of the BD’s type vascular dementia verified by postmortem histological examination. It is known that age is an unmodified risk factor for cardiovascular disease. However, in recent decades there has been “vascular risk rejuvenation” of the world, which calls for the development and improvement of approaches to screening and clinical examination of these contingents. The presented case report demonstrates the difficulty in the diagnosis of this pathology of the brain and demonstrates the need for inclusion of the BD in a number of differential diagnostic in patients with cerebrovascular diseases. In addition, we believe that dementia screening should include medical and psychological counseling of patients at risk.

Purpose: to review the available data on molecular-genetic diagnostic and prognostic markers in prostate cancer. Material and methods. The following electronic databases were used for our systematic review: Medline, Cochrane Library and Elibrary. Of 540 studies, 61 were used for our systematic review. Results. There are currently a variety of both prognostic and diagnostic markers used for diagnosis and treatment of prostate cancer. The review presents the classification of markers depending on the method and medium in which they were identified. The molecular mechanisms of participation of the different genes and proteins in the pathogenesis and progression of prostate carcinoma were analyzed and the potential importance of their use in clinical practice was provided. Conclusion. Many of the existing markers can be used for screening and early detection of tumors, and they have been proved to have a prognostic value. However, contradictory findings with regard to certain proteins and genes require further study, their validation with the subsequent implementation into clinical practice.

We present a case report of locally advanced colorectal cancer that responded successfully to conservation chemotherapy allowing R resection to be performed. Morphological characteristics prior to and after chemotherapy have been described in detail. This case report demonstrates the feasibility of performing radical treatment for patients with locally advanced rectal cancer using neoadjuvant chemotherapy.

Overexpression of ABC drug transporters can cause multidrug resistance (MDR) in cancer cells, which is a major obstacle in the success of cancer chemotherapy. Our study revealed a correlation between the expression of invasive breast cancer resistance-associated proteins, such as P-glycoprotein (ABCB1), MRP2 (ABCC2), BCRP (ABCG2) in tumor cells and pathologic response to neoadjuvant chemotherapy. The response to neoadjuvant chemotherapy was shown to be associated with a lack of BCRP expression in tumor cells. The pathologic tumor response was correlated with the presence of positive MRP2 expression and the expression level of P-glycoprotein in cells of invasive breast cancer.

The paper is devoted to the study of the expression of markers associated with invasive breast carcinoma. The study included a surgical material from 107 patients with invasive carcinoma of the non-specific type of breast cancer who had not previously received neoadjuvant therapy. The study revealed a number of markers related to invasive tumor growth, characterized by a pronounced heterogeneous expression pattern in all cases. Study of the expression of markers associated with invasive breast carcinoma showed that not all cells are able to promote invasive growth in different periods of time, but the fact of detecting the positive expression of the markers in tissue tumors indicates a more aggressive cancer phenotype with a high potential for invasion.

Treatment outcomes of soloid-pseudopapillar tumor of the pancreas in a young woman have been presented. Soloid-pseudopapillar tumor of the pancreas is a rare neoplasm. As a rule, it is detected by chance during routine screening US examinations. Diagnosis is frequently delayed and tumor size at presentation is frequently large. In case of systic pancreatic lesion, soloid-pseudopapillar tumor should be considered in the diagnosis. As a low-grade malignancy, the tumor seldom recurs and metastasizes.

The present study has found significant heterogeneity of luminal A breast cancer group, which is manifested by differences in relationship between the frequency of lymphogenic metastasis and morphologic and molecular-biological parameters of the primary tumor. The frequency of regional metastases has appeared to relate to the presence of microalveolar structures in infiltrating component of invasive ductal breast cancer and to its phenotypic variety only in menopausal patients. It can be evidence of differences in tumor pathogenesis in patients with different state of menstrual function even within one molecular-genetic tumor group. It is important to emphasize that the different variantsof clinical behavior of luminal A breast cancer are associated with morphological parameters of the tumor, allowing one to easily obtain the additional information during histological examination of bioptic material for predicting clinical course of luminal-type A breast cancer.

Luminal A breast cancer has been shown to be characterized by the marked morphological heterogeneity. It is manifested by the variety of the infiltrative component structure of the primary tumor in which different structure types vary widely. The frequency of metastaticinvolvement of lymph nodes has appeared to associate with a variety of infiltrative component of the tumor and the presence of microalveolar structures in it. Neither morphological patterns of the lesion nor parameters of lymphogenic metastasis were associated with hematogenous dissemination, thus allowing no them to be considered as prognostic criteria.

Hormone therapy with tamoxifen is the commonly used treatment for luminal breast cancer. However, it appears to be ineffective in 20–40 % of cases and the possible reasons of this failure are related to the features of distribution and structure of estrogen receptor alpha (ERα) in tumor tissue. Realization of the therapeutic effect of tamoxifen is carried out by blocking the activation center of AF-2 receptor. The change in the functional state of this receptor resulted from single-nucleotide polymorphisms coding 2228480 (G/A) in exon 8 of ERα gene is considered as a possible cause of treatment failure with tamoxifen.The purpose of the study was to analyze the relationship between the ERα expression and polymorphic variants in exon 8 of the ERα gene and the efficacy of tamoxifen in patientswith luminal breast cancer.Material and methods: The study included 97 patients with stage T1–2N0–1M0 luminal breast cancer, who received adjuvant chemotherapy with tamoxifen. The follow-up ranged from 24 to 130 months. Long-term treatment outcomes were assessed upon the progression of the disease with the evidence of distant metastases. In tumor tissue samples, the ERα expression was studied using the immunohistochemical method. The values of the ERα expression intensity as well as the character of ERα distribution were assessed. Polymorphic variants of exon 8 of the ERα gene were studied using real-time PCR.Results. The heterogeneous distribution of ERα gene was observed in 86.5 % cases with diseases progression and in 58.3 % of cases with favorable disease outcome (р=0.0072; χ2 =7.22). Mutation of rs2228480 (G/A) in exon 8 of the ERα gene was observed in 19.4 % of cases. Mutations were not noted in tumor cells with homogenous distribution of the ERα gene and mutations were found in 25.7 % (р=0.014; χ2 =6.09) in heterogeneous distribution. Mutation in exon 8 of the ERα gene was shown to occur more often in patients with disease progression (р=0.01; χ2 =6.52).Conclusion: The character of the ERα gene distribution and the presence of mutation in exon 8 of the ERα gene in tumor tissue can be considered as additional predictive factors of response to therapy with tamoxifen in patients with luminal breast cancer.

Problems in diagnosis and treatment of small intestine cancer are related to the rarity of the disease as well as to the non-specificity of clinical signs and symptoms. This case report describes difficulties in diagnosis of adenocarcinoma of the ileum

The results of surgical treatment of a rare disease – retroperitoneal lymphangiomyomatosis ray data and morphological studies.

Background. The paper has been devoted to the study of clinical and morphological features of bilateral breast cancer (BC). Despite the increased interest in the lateral BC, pathogenesis of this type of cancer have been little studied. Мaterials and methods. Clinical and morphological parameters were studied in 600 patients with unilateral and bilateral breast carcinoma. Results. Synchronous and metachronic bilateral breast cancer is characterized by more pronounced heterogeneity of the morphological structure with the frequent presence of discrete groups of tumor cells and ductal structures in the tumor node as compared to unilateral breast cancer. Synchronous bilateral breast cancer has a favorable clinical course and is mainly represented by the luminal A molecular genetic type. Metachronous bilateral breast cancer is often characterized as a triple negative and luminal B type with high proliferative activity and is associated with poor prognosis. There is a difference in prognostic parameters of lymphogenous and hematogenous metastasis between synchronous and metachronous breast cancer. For synchronous bilateral breast cancer, morphological parameters can serve as prognostic factors of hematogenous and lymphogenous metastasis. For metachronous breast cancer, prognosis of hematogenous metastasis is associated with severity of lymphogenous metastasis. Conclusion. The data obtained allow us to determine the typical clinical and morphological features of synchronous and metachronous bilateral breast cancers, as well as to identify additional prognostic parameters of tumor progression.

Presented modern literature data on the features of the pathogenesis, course, clinical and morphological expression and tumor characteristics, parameters and nodal metastasis of hematogenous bilateral breast cancer. Highlight the results of domestic and foreign studies in recent years to determine the prognostic factors and recurrence of synchronous and metachronous bilateral breast cancer. It was revealed that the frequency of bilateral breast tumor lesions varies widely, ranging from 0.1 to 20%, with metachronous tumors recorded significantly higher (69.6% ) than the synchronous (22.7%). The probability of occurrence of metachronous breast cancer is higher in women with a family history, as well as if they have a gene mutation BRCA-1. Found that the most common histological type of breast tumor with bilateral lesions is invasive ductal. However, the incidence of invasive lobular cancer and non-invasive lobular cancer is slightly higher among synchronous bilateral cancer compared with unilateral disease. Studies have shown that in a double-sided synchronous breast cancer tumor, as a rule, has a lower degree of differentiation, and the higher the expression level of estrogen receptors and progesterone receptors. Relevance of the issue because the identification of patterns in the study of lymphatic and hematogenous features bilateral metastasis of mammary tumors provides a basis for speculation about the differences in the progression of neoplastic disease in these groups and is a cause for further detailed research in this area to identify and evaluate the prognosis and also the choice of tactics of such patients.

We studied the course of the disease in 114 patients with invasive ductal breast cancer stage T1-4N03M0, held a combined treatment at the Department of General Oncology FGBU Cancer Research Institute of Oncology, SB RAMS in the period from 2000 to 2007. Revealed additional information of importance for the prediction of hematogenous dissemination in patients with different molecular-genetic types of breast cancer. Predict this worst-case flow of tumor on the basis of information about the regional lymph nodes is possible only with triple negative breast cancer, and only in patients who are in a state of menopause.

Schilder’s leukoencephalitis was described by American neurologist and psychiatrist P.F. Schilder (1886– 1940). At present the pathology is regarded as acute diffuse form of multiple sclerosis, and it is characterized by demyelination of the brain. Clinical manifestations of pathological process varied. The disease is a rare, usually in children and adolescents. In patients older than 40 years of death can occur in a period of 6 months to 3 years from the onset of the first symptoms. Considering the rarity of the disease, we present a clinical case with autopsy data from our practice.