TRPS1 (Tricho-rhino-phalangeal syndrome type 1) - a transcription factor of the GATA family, has recently emerged as a promising immunohistochemical marker for breast cancer. This review summarizes current data on the diagnostic, prognostic, and potential therapeutic relevance of TRPS1, as well as its molecular functions and expression patterns across different breast cancer subtypes. TRPS1 demonstrates high sensitivity, including in diagnostically challenging cases such as triple-negative and poorly differentiated carcinomas, where traditional markers (GATA3, mammaglobin) may be absent or weakly expressed. The advantages of TRPS1 in the differential diagnosis of metastatic lesions and its possible role in prognostic panels are highlighted. Methodological limitations of the using marker, standardization needs and future perspectives for clinical implementation are also discussed in article.

The genes of mismatch repair system (MMR) are responsible for correcting errors in DNA replication. MMR defects (dMMR) lead to mutations in microsatellites - repetitive nucleotide base sequences - resulting in microsatellite instability (MSI). Determination of dMMR/MSI status in tumors is an important factor for the development of patient management tactics, as the dMMR/MSI phenotype serves as both a marker of favorable prognosis and a predictor of response to immunotherapy in tumors of many localizations. MMR status is assessed via immunohistochemistry (IHC) on histological material. However, in some cases heterogeneity of intratumoral MMR protein expression (MMR heterogeneity) becomes an obstacle to this. MMR heterogeneity (areas of weak/absent staining on the background of normal expression) is poorly studied, especially in gastric cancer, in contrast to colorectal cancer and endometrial cancer. The lack of a methodology for interpreting this phenomenon leads to significant difficulties in stratifying patients who are indicated for dMMR/MSI status determination. The article systematizes current data on MMR heterogeneity in gastric cancer and tumors of other localizations, discusses molecular mechanisms, clinical significance and recommendations to overcome diagnostic limitations.

This study analyzes the modern (2021) WHO classification of lung tumors and reviews publications in Russian and English from databases including PubMed, Google Scholar, ClinicalTrials.gov, eLibrary, and CyberLeninka. The aim of this review is to identify key changes in the 2021 WHO classification compared to the 2015 edition and assess their significance for the diagnosis and personalized treatment of non-small cell lung cancer. Special attention is given to the handling of small biopsy specimens, which requires an integrated approach involving morphological examination, immunohistochemistry, and molecular genetic testing.

The epidermal growth factor receptor (EGFR) is among the research subjects of most interest and remains genuinely attractive due to its key role in regulating the main conserved signaling pathways responsible for cell growth, survival, and proliferation. Dysregulation of the signaling pathways leads to cell malignant transformation, tumor progression, and metastasis. Therefore, EGFR is considered as one of the main targets for anticancer drug development. Although several generations of novel anti-EGFR drugs have been successfully developed, acquisition of drug resistance and the mutation status of the downstream effector protein KRAS significantly reduce the tumor response to therapy. The review focuses on the current approaches to anti-EGFR therapy. Drugs designed to block the EGFR-mediated signaling are described, including monoclonal antibodies, tyrosine kinase inhibitors, and immunotoxins. Mechanisms of acquired resistance to anti-EGFR therapy are discussed, and combination treatment strategies are proposed to improve the efficacy of the available drugs. Finally, promising antitumor agents, including ribonucleases (RNases) of various origins, are considered.

Colorectal cancer remains one of the leading causes of cancer-related mortality, highlighting the importance of optimizing approaches for its early diagnosis and therapy. One promising area in this field is the investigation of the role of the gut microbiome in the initiation and progression of colorectal cancer. This review examines three principal hypotheses explaining the contribution of microbiota to carcinogenesis: the "Alpha-bug", the "Keystone pathogen", and the "Driver-Passenger" models. We analyze data on the mechanisms of microbiota-tumor cells interactions, including the induction of inflammation, genotoxicity, and disruption of the intestinal barrier function. Findings are also presented indicating that certain microorganisms previously considered markers of the advanced stages may possess pro-oncogenic properties, thereby refining existing carcinogenesis models. Overall, the data suggest that the microbiota and its dysbiotic alterations can be considered potential targets for colorectal cancer diagnosis and therapy.

Primary central nervous system lymphoma is a rare type of extranodal non-Hodgkin's lymphoma that occurs primarily in the central nervous system and represented by diffuse B-cell large cell lymphoma. Despite the fact that this tumor has been known for almost 100 years, studying it is difficult due to the rarity and, consequently, the limited number of statistically significant samples for research. This review analyzes the available literature data on the biological features of primary central nervous system lymphomas, pathogenesis and tumor microenvironment. In addition, we analyzed prognostic factors and current treatment strategies. The objective of this review is to determine the prospects for further study of this tumor.

Adenocarcinoma and adenosquamous carcinoma of the cervix together account for up to 20% of all cervical cancers. These histologic subtypes are characterized by a worse prognosis compared with squamous cell cancer of the same grade and have specific epidemiologic, morphologic and molecular features. Despite fundamental differences, therapeutic approaches for cervical cancer are similar regardless of tumor histology. This article discusses promising companion diagnostic markers for cervical cancer treatment, including MSI, PD-L1 and TIL's, that may find application in the therapy of prognostically unfavorable subtypes of cervical cancer. The literature review revealed that despite the low frequency of immunotherapy markers among adenocarcinomas and adenosquamous carcinomas of the cervix, analyzing them will allow us to identify a group of patients who will benefit most from immunotherapy, a key step towards improving treatment outcomes.

The discovery of a class of long noncoding RNAs (lncRNAs), including lncRNAs of the small nucleolar RNA (snoRNA) host gene family, SNHG, has led to growing interest in the study of both snoRNAs themselves and the genes encoding them. Currently, of the 232 known snoRNA genes, only 32 have been confirmed to have lncRNAs. At the same time, a positive correlation has been shown between the expression of lncRNAs and snoRNAs encoded by a common host gene of the SNHG family. Thus, lncRNA of the SNHG1 gene correlates with snoRNAs SNORD22 and SNORD25-31, and lncRNA of the SNHG16 gene, with snoRNAs SNORD1A, SNORD1B, and SNORD1C. There is evidence that SNHG lncRNAs can participate in oncogenesis both through regulatory functions inherent to lncRNAs and by influencing ribosome biogenesis. At the same time, information has accumulated on the "extraribosomal" functions of snoRNAs. In addition to a brief excursion into the biological functions of snoRNAs and SNHG lncRNAs, we present a comprehensive review of data on the role of these two types of noncoding RNAs in the pathogenesis of ovarian cancer, the most insidious cancer of the female reproductive system. The influence of these regulatory RNAs on the main processes of ovarian oncogenesis, such as apoptosis, epithelial-mesenchymal transition, cell cycle control, and DNA methylation mechanisms in this type of cancer is considered. The prospects for clinical application of regulatory RNAs due to their influence on the level of drug resistance are also discussed.

Breast cancer (BC) is a multifactorial disease that is characterized by various genetic and epigenetic changes that occur due to the effect of various factors including that of environmental etiological agents. The obtained scientific data speak volumes for epigenetic dysregulation in BC pathogenesis. Out of all epigenetic markers, various microRNA regulating a wide spectrum of biological processes in a cell could be viewed as one of the predictors of potential risk. Understanding the functional role of these molecules will provide valuable information about the complex molecular mechanisms underlying the appearance and development of BC. This review summarizes currently existing publicly available data on aberrant expression of miR-125b, miR-181a, and miR-16 in case of various cancer localizations; analyzes their role in BC pathogenesis; presents an annotation of the target-genes; and evaluates the repression potential of microRNA and their diagnostic significance in case of BC. An analysis of changes in miRNA expression during radiation exposure was conducted. Interest in examining specific miRNAs is due to the results of long-term monitoring of the health of people living in radioactively contaminated areas of the Southern Urals, as well as data on the expression profiles of miR-125b, miR-181a, and miR-16 over the long term in exposed people.

Breast cancer (BC) with triple-negative molecular profile is characterized by special and rather serious problems in terms of clinical management of patients compared to other types. On the one hand this is due to the fact that tumors with such a status often do not respond to routine targeted therapy and only a minimal number of drugs are currently available for their treatment. On the other hand, cases of triple-negative BC (TNBC) are often diagnosed against the background of an extensive metastatic process, in which confirmation of the metastases histogenesis to breast tissue is a difficult task due to the low sensitivity of such carcinomas to specific organ markers. It is known that about 40-50% of all TNBC cases are characterized by the achievement of complete pathomorphological regression of the primary tumor as a result of neoadjuvant chemotherapy courses, which determines a favorable prognosis of the disease. In other cases (also up to 50%), TNBC do not respond to chemotherapy and exhibit persistent drug resistance, such tumors are more aggressive, have the highest relapse rate and a high risk of metastasis. For this group of patients, the issue of finding predictive markers and new therapeutic methods remains unresolved. The presented literature review reflects the data of the analysis of publicly available results of scientific studies devoted to potentially promising molecular markers, including IDO1, DCLK1 and FOXC1, their significance in BC, including TNBC is described. Based on the analysis of literary data, it can be argued that IDO1, DCLK1 and FOXC1 are promising objects for further research in the context of TNBC. Each marker has unique characteristics that make them important both for disease prognosis and for the development of new therapeutic approaches.

Solitary fibrous tumor is a rare mesenchymal neoplasm, the most common localization of which is the pleural cavity, but the tumor can also affect other organs. This neoplasm with localisation in the kidney was first described only in 1996. Solitary fibrous tumor accounts for 0.2% of all kidney neoplasms and is an exceptional phenomenon. Currently, there is no generally accepted theory explaining the etiology and pathogenesis, probably, its development is a multifactorial process including a combination of genetic, epigenetic and external factors. Despite the lack of unambiguous opinion on the nature of the neoplasm, the spectrum of molecular abnormalities in this tumor has been sufficiently studied. The literature presents a limited number of publications devoted to this pathology, in this regard it should be noted that in routine practice, the morphological picture may not always be so unambiguous and require the pathologist to conduct differential diagnostics with a fairly wide range of tumors. Given the rarity of this disease, we would like to share a description of our own clinical observation demonstrating the possible difficulties of morphology diagnostics.

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor. SFT was first described by Klemperer and Rabin in 1931. They described a fibrous tumor of the pleura. Currently, isolated cases of SFT of the gallbladder and common bile duct have been described in the world. SFT is characterized by nuclear expression of STAT6 and the formation of chimeric genes NAB2-STAT6. A case report of a rare SFT of the common bile duct in a 66-year-old patient is presented. The description contains data from radiation and ultrasound diagnostic methods, macro- and microscopic characteristics of the tumor and immunohistochemical characteristics.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by autonomous secretion of parathyroid hormone by altered parathyroid glands. In most cases PHPT is a sporadic disease, 5-10% of observations are genetically determined syndromal and non-syndromal forms. Studies of families with hereditary forms of PHPT have led to the discovery of key oncosuppressor genes and proto-oncogenes whose somatic mutations underlie the development of many sporadic parathyroid tumors. Another interest in the pathogenesis of primary hyperparathyroidism is studying mechanisms of epigenetic regulation in tumor tissue. In the first part of this review, we will discuss the classification, morphology, and etiology of PHPT. In the second part, we will present a summary of the most important studies using genetic analysis, classified according to the method used.

Gastric cancer remains the fifth most common malignant neoplasm in the world and ranks fifth among the causes associated with cancer. The TNM system remains the gold standard for predictive stratification of patients with gastric cancer, but the search for new sensitive, specific and reproducible biomarkers to develop a personalized approach to the management of patients with gastric cancer does not lose its relevance. The phenomenon of tumor budding is a well-established independent prognostic factor in colorectal cancer. In 2017, the first guideline on the method of calculating tumor budding for colorectal cancer was published. Despite the promising potential of using tumor budding in gastric cancer this parameter is still not evaluated in everyday practice. This lection provides data on various methods of counting tumor budding in gastric carcinomas, describes the molecular mechanisms of interaction between tumor cells and the immune microenvironment, and summarizes the available data on the relationship of clinical and morphological characteristics of gastric cancer with the degree of tumor budding. The relationship between the degree of tumor budding and the prognostic characteristics of gastric cancer and the prospects for its use is also described.

In 2021, a new type of tumor was defined according to the new WHO classification (high-grade astrocytoma with piloid features, HGAP). Morphological and neuroimaging differences of HGAP from pilocytic astrocytoma complicate diagnosis. Now, significant detection of this tumor is possible only using molecular genetic testing, in particular, methylation profile analysis.

Dimethylarginine Dimethylaminohydrolase 1 (DDAH1) is an essential enzyme capable of degrading asymmetric dimethylarginine, which is an endogenous inhibitor of nitric oxide synthase. Increased expression of DDAH1 and subsequent increased NO production are associated with carcinogenesis. In particular, DDAH1 is involved in the creation of a vascular network by tumor cells, vasculogenic mimicry, which is closely associated with tumor progression and poor patient prognosis. This is the reason why DDAH1 may be a potential therapeutic target for the treatment of cancer.

Plexiform fibromyxoma (PFM) and gastroblastoma (GB) are rare gastric tumors with a specific MALAT1::GLI1 rearrangement, included in the conditional spectrum of neoplasms with alterations of the GLI1 gene. The article presents a clinical case of PFM in a 6-year-old girl and a literature review highlighting current data on the morphology, immunophenotype and molecular genetic characteristics of PFM and GB. Despite the common genetic anomaly, differences in the morphology and clinical course of these tumors indicate the need for further research to clarify their relationship and potential reclassification in the light of new data on tumors with GLI1 gene abnormalities. Integrating the accumulated knowledge about tumors with GLI1 gene alterations into diagnostic algorithms and therapeutic approaches will help improve the treatment outcomes of patients with these rare neoplasms.

Oncolytic viruses represent a promising class of immunotherapeutic agents for the treatment of malignant tumors. The proposed mechanism of action of various oncolytic viruses has initially been explained by the ability of such viruses to selectively lyse tumor cells without damaging healthy ones. Recently, there have emerged more studies determining the effect of the antiviral immunostimulating mechanisms on the effectiveness of treatment in cancer patients. Stimulation of innate immune cells by an oncolytic virus can initiate an adaptive antitumor immune response, yet at the same time, the antiviral mechanisms of the immune system can limit the spread of the virus, thereby reducing its effectiveness. Thus, the success of the clinical application of the oncolytic viruses directly depends on the three key components: tumor immunosuppression, antiviral responses, and antitumor immune responses. The review presents current data on the influence of pattern recognition receptors on the effectiveness of oncolytic viruses.

The purpose of this review was to analyze the most perspective methods for risk stratification of malignant transformation of pancreatic intraductal papillary mucinous neoplasms (IPMN). Advisability of humoral predictors (tumor markers, inflammatory markers, circulating leptin and branched-chain amino acids, etc.) is in identifying prognostic signs suitable for risk stratification of IPMN malignant transformation and, therefore, determining treatment strategy for a particular patient. According to data screening, the most advisable predictors of malignant transformation of neoplasms are carbohydrate antigen 19-9, carcinoembryonic antigen, neutrophil-to-lymphocyte ratio and high-grade dysplasia. At the same time, DNA sequencing, analysis of miRNA and telomere expression, as well as liquid biopsy have a high potential and require further research for routine clinical practice.

The bony fish Danio rerio (zebrafish) has become one of the important vertebrate model organisms in biomedical cancer research and is used, among other things, for the development of anticancer drugs using xenotransplantation approaches. The ex utero development of zebrafish, optically transparent tissues in the first month of growth, and the immature adaptive immune system during this period greatly facilitate the manipulation of embryos. For highly aggressive cancers where patient survival may be expected to be only a few months, a zebrafish xenograft assay may be the only appropriate method as it requires only four to seven days. Thousands of embryos can be implanted with biopsy tissue from a patient to produce zebrafish xenografts and to use them to screen a large number of drugs and compounds automatically to develop an effective treatment regimen for a specific patient. This review examines the advantages and disadvantages of the zebrafish model in oncology research. The main focus is on the use of zebrafish xenografts to study metastasis and to create avatars in personalized medicine.