Cisplatin (DDP) is widely used in the chemotherapy of cervical cancer (CC), the fourth most common female malignancy worldwide. However, some patients progress to chemotherapy resistance, which leads to chemotherapy failure, tumor recurrence, and poor prognosis. Therefore, strategies to identify the regulatory mechanisms underlying CC development and increase tumor sensitivity to DDP will help improve patient survival. This research was designed to ascertain the mechanism of EBF1-dependent regulation of FBN1 which promotes chemosensitivity of CC cells. The expression of EBF1 and FBN1 was measured in CC tissues resistant or sensitive to chemotherapy and in DDP-sensitive or -resistant cells (SiHa and SiHa-DDP cells). SiHa-DDP cells were transduced with lentiviruses encoding EBF1 or FBN1 to evaluate the influence of these two proteins on cell viability, expression of MDR1 and MRP1, and cell aggressiveness. Moreover, the interaction between EBF1 and FBN1 was predicted and demonstrated. Finally, to further verify the EBF1/FB1-dependent mechanism of DDP sensitivity regulation in CC cells a xenograft mouse model of CC was established using SiHa-DDP cells transduced with lentiviruses carrying EBF1 gene and shRNA directed to FBN1 EBF1 and FBN1 showed decreased expression in CC tissues and cells, particularly in those resistant to chemotherapy. Transduction of SiHa-DDP cells with lentiviruses encoding EBF1 or FBN1 lead to decreased viability, IC50, proliferation capacity, colony formation ability, aggressiveness, and increased cell apoptosis. We have shown that EBF1 activates FBN1 transcription by binding to FBN1 promoter region. Additionally, it was revealed that FBN1 silencing reversed the promoting effect of EBF1 overexpression on chemosensitivity of CC cells in vivo. EBF1 facilitated chemosensitivity in CC cells by activating FBN1 transcription.

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of cancers that differ in pathogenesis and prognosis. The main methods of treating NHL include chemotherapy, immunochemotherapy, and radiation therapy. However, a significant proportion of these tumors are chemoresistant or rapidly recur after a short chemotherapy-induced remission. In this regard, the search for alternative cytoreductive therapeutic methods is relevant. Aberrant expression of microRNA (miRNA) is one of the mechanisms responsible for the emergence and progression of malignant lymphoid neoplasms. We analyzed the profile of miRNA expression in the biopsy material from lymph nodes affected by diffuse large B-cell lymphoma (DLBCL). The key material of the study was histological preparations of lymph nodes obtained by excisional diagnostic biopsy and treated using conventional histomorphological formalin fixation methods. The study group consisted of patients with DLBCL (n = 52); the control group consisted of patients with reactive lymphadenopathy (RL) (n = 40). It was shown that the miR-150 expression level in DLBCL was reduced by more than 12 times (</>p = 3.6 x 10^(-15)) compared with RL. Bioinformatics analysis revealed the involvement of miR-150 in the regulation of hematopoiesis and lymphopoiesis. The data we obtained allow us to consider miR-150 as a promising therapeutic target with great potential in clinical practice.

CIC-rearranged sarcoma is a rare and extremely aggressive tumor that occurs mainly in soft tissues. Despite the fact that identification of a characteristic genetic rearrangement is necessary to verify the diagnosis, in most cases, the correct diagnosis can be made by comparing histological signs and a characteristic immunophenotype, which greatly speeds up the diagnosis. The article describes a case of CIC-rearranged sarcoma in a 14-year girl with the successful application of the CWS-2009 treatment protocol.

Assessment of FGFR2 status in gastric cancer is an important task, without clarification of which it is impossible to identify a cohort of patients in whom the best response to treatment with anti-FGFR2 drugs could be obtained.

Differential diagnosis of supratentorial ependymomas is of particular difficulty in neurooncology due to nonspecific clinical and radiographic findings, a rare seen «classic» morphological picture, and a nonspecific immunophenotype. Thanks to molecular genetic methods, in particular real-time PCR, it has become possible to verify supratentorial ependymomas and identify their molecular group, on which further prognosis depends.

Peutz-Jeghers syndrome (PJS) is a rare hereditary syndrome characterized by the growth of hamartomatous polyps in the gastrointestinal tract, perioral pigmentation and an increased risk of malignant neoplasms. The syndrome is caused by a pathogenic variant in the STK11 gene.

In 2022, the Quality Control Center for Immunohistochemical Studies of the Russian Medical Academy of Continuing Professional Education conducted 12 rounds of markers for breast, lung, prostate, bladder cancer with the participation of 83 laboratories. For the first time, a round was held to control the method of in situ hybridization in the diagnosis of breast cancer, and a digital round. Typical problems in carrying out immunohistochemical studies in oncomorphology have been identified and the importance of participation of laboratories in external control has been shown.

This article presents a case of successful treatment of inoperable gastric cancer with impaired mismatched nucleotide repair system (dMMR/MSI-H) in a 72-year-old patient. In view of age, somatic status and the presence of comorbidity, it was decided to prescribe anti-PD-1 therapy in the 1st line of treatment. Currently, after a 2-year course of treatment, the patient is in stable remission.

Intracranial meningeal solitary fibrous tumors (SFT) originating from mesenchymal tissue are much less common than those with lesions of the visceral pleura or liver and were isolated as a nosological form only in 1996. These tumors are identical in clinical manifestations, MRI and light microscopy data to meningiomas. The pathognomonic difference of SFT, according to the 5th edition of the WHO classification, is the detection of overexpression of the protein encoded by the STAT6 gene. Estimation of other immunohistochemical markers is variable. At the same time, SFT has a tendency to more frequent recurrence and delayed malignancy. Transitional forms are possible. To form a clearer nosological outline of the SFT, it is necessary to accumulate clinical observations. A case of a giant meningioma of the posterior cranial fossa, which recurred 18 years after total removal at a 5-year annual control, is presented. Light microscopy of both primary and recurrent tumors revealed fibrous meningioma (WHO GI). Immunohistochemically revealed diffuse overexpression of CD34 and CD99. Determining the expression of the STAT6 protein was not technically possible. This case is regarded as a meningioma of the posterior surface of the pyramid of the temporal bone, growing into the cavity of the IV ventricle, with late recurrence without malignancy, with specific immunohistochemical profile.

To study the somatic mutational status of the FGFR3 gene in urothelial bladder cancer (BC) and evaluate its relationship with the clinical and morphological characteristics of the tumor, deficiency of the DNA mismatch repair (dMMR), PD-L1 tumor status, and immunohistochemical (IHC) expression of the p16 protein.

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that removes various adducts from the 3' end of DNA. Such adducts are formed by enzymes that introduce single-strand breaks in DNA during catalysis (for example, topoisomerase 1) and a number of anticancer drugs with different mechanisms of action. Poly(ADP-ribose) polymerase 1 (PARP1) is an enzyme that catalyzes posttranslational modification (PARylation) of various targets and thus controls many cell processes, including DNA repair. Tdp1 is a PARP1 target, and its PARylation attracts Tdp1 to the site of DNA damage. Olaparib is a PARP1 inhibitor used in clinical practice to treat homologous recombination-deficient tumors. Olaparib inhibits PARylation and, therefore, DNA repair. The Tdp1 inhibitor OL7-43 was used in combination with olaparib to increase the antitumor effect of the latter. Olaparib cytotoxicity was found to increase in the presence of OL7-43 in vitro. OL7-43 did not exert a sensitizing effect, but showed its own antitumor and antimetastatic effects in Lewis and Krebs-2 carcinoma models.

One of the most common malignant liver diseases is hepatocellular carcinoma, which has a high recurrence rate and a low five-year survival rate. It is very heterogeneous both in structure and between patients, which complicates the diagnosis, prognosis and response to treatment. In this regard, an individualized, patient-centered approach becomes important, in which the use of mimetics and hsa-miRNA inhibitors involved in the pathogenesis of the disease may be determinative. From this point of view hsa-miRNAs are of interest, their aberrant expression is associated with poor prognosis for patients and is associated with tumor progression due to dysregulation of programmed cell death (apoptosis). However, the effect of hsa-miRNA on tumor development depends not only on its direct effect on expression of genes, the primary targets, but also on secondary targets mediated by regulatory pathways. While the former are actively studied, the role of secondary targets of these hsa-miRNAs in modulating apoptosis is still unclear. The present work summarizes data on hsa-miRNAs whose primary targets are key genes of the extrinsic pathway of apoptosis. Their aberrant expression is associated with early disease relapse and poor patient outcome. For these hsa-miRNAs, using the software package ANDSystem, we reconstructed the regulation of the expression of secondary targets and analyzed their impact on the activity of the extrinsic pathway of apoptosis. The potential effect of hsa-miRNAs mediated by action on secondary targets is shown to negatively correlate with the number of primary targets. It is also shown that hsa-miR-373, hsa-miR-106b and hsa-miR-96 have the highest priority as markers of hepatocellular carcinoma, whose action on secondary targets enhances their anti-apoptotic effect.

Personalization of gastric cancer (GC) treatment is an urgent problem because of the clinical heterogeneity and aggressive course of the disease. Four GC subtypes were isolated based on molecular characteristics by The Cancer Genome Atlas researchers in 2014: Epstein-Barr virus positive (EBV^(+)), microsatellite unstable (MSI), chromosomally unstable (CIN), and genomically stable (GS). There is no unified method to detect the CIN and GS subtypes today, while MSI and EBV status assessments are used routinely and are of great clinical importance. A total of 159 GC samples were tested for MSI, EBV DNA, and somatic mutations in codons 12-13 (exon 2), 61 (exon 3), and 146 (exon 4) of the KRAS gene; codons 597-601 (exon 15) of the BRAF gene; and codons 542-546 (exon 9), 1047-1049 (exon 20) of the PIK3CA gene. EBV^(+) GC was detected in 8.2% of samples; and MSI, in 13.2%. MSI and EBV+ were found to be mutually exclusive. The mean ages at GC manifestation were 54.8 and 62.1 years in patients with EBV^(+) and MSI GCs, respectively. EBV^(+) GC affected men in 92.3% of cases, 76.2% of the patients were older than 50 years of age. Diffuse and intestinal adenocarcinomas were diagnosed in 6 (46.2%) and 5 (38.5%) EBV^(+) cases, respectively. MSI GC equally affected men (n = 10, 47.6%) and women (n = 11, 52.4%). The intestinal histological type was the most prevalent (71.4%); the lesser curvature was affected in 28.6% of the cases. The E545K variant of PIK3CA was observed in one EBV^(+) GC case. A combination of clinically significant variants of KRAS and PIK3CA was found in all MSI cases. The BRAF V600E mutation, which is specific to MSI colorectal cancer, was not detected. The EBV^(+) subtype was associated with better prognosis. The five-year survival rates were 100.0 and 54.7% for MSI and EBV^(+) GCs, respectively.

Parathyroid cancer (PTC) is usually sporadic; however, it could be presented as a component of hereditary syndromes. The prevalence of PTC among patients with primary hyperparathyroidism (PHPT) is about 1% cases. The lack of reliable preoperative predictors significantly complicates the diagnosis of PTC. The clinical course is non-specific and in most cases is determined by severe hypercalcemia. The final diagnosis can only be made on the basis of invasive histopathologic features, while an analysis immunohistochemical (IHC) one can be used only as an additional method. Given the rarity the diagnosis of MEN1-related PTC a challenge. We present two clinical cases of patients with PTC and a verified heterozygous mutation in the MEN1 gene. The described cases demonstrate the complexity of morphological diagnosis for PTC, the heterogeneity of clinical manifestations in patients with the MEN1 mutation, as well as the need for timely screening to identify other components of MEN1 syndrome and mutations of the MEN1 gene among first-line relatives.

At the beginning of this century, there was a paradigm shift in understanding the histogenesis of high-grade serous carcinomas. The theory of the origin of these tumors from the ovarian surface epithelium was replaced by the concept of their origin from the secretory epithelium of the fallopian tubes. In recent years, researchers have put forward the hypothesis of the "escape" of the precursor of high-grade serous carcinomas. It allows looking at the carcinogenesis of these neoplasms as a natural history of tumor transformation of the serous epithelium without reference to a specific localization.

Stomach cancer continues to be a global health problem, ranking 5th among cancers and 4th among the causes of death from cancer in the world. Autoimmune atrophic gastritis is a chronic autoimmune disease characterized by the production of antibodies to parietal cells and intrinsic factor, followed by atrophy of the mucous membrane of the body and fundus of the stomach. Chronic autoimmune inflammation can lead to damage to the genetic apparatus of the cell and trigger a multi-stage process of carcinogenesis. Our article presents an unusual case of three different gastric tumors, including adenocarcinoma with microsatellite instability, in a patient with autoimmune gastritis.

Using the example of a recurrent tumor with a 10-year follow-up, the authors show that mutation of the IDH1/2 genes in astrocytomas is not always an early event in the pathogenesis of glioma, that in rare cases a 1p19q codeletion can be found in astrocytomas, and that IDH-mutant tumors can occur in childhood.

Microsatellite instability, which is caused by a deficiency in the DNA unpaired nucleotide repair system, is an important pathogenetic event for some tumors. In addition, the detection of this molecular feature becomes an independent prognostic factor in the course of the disease and a predictor for the appointment of therapy with immune checkpoint inhibitors. Immunohistochemistry is a reliable and available method for detecting a deficiency in the DNA mismatch repair system, and it has recommended as a screening for hereditary syndromes associated with microsatellite instability. This article discusses the advantages and disadvantages of this research method from the point of view of the practitioner.

Anomalies of the FOXO1 gene in alveolar rhabdomyosarcoma are associated with a worse clinical prognosis, which determines the high value of studying the status of this gene when choosing a therapy strategy. The «gold standard» for determining FOXO1 gene rearrangements is currently the fluorescent in situ hybridization (FISH) technique.

To study the relationship of NMDA receptors expression activity with proliferative activity and genetic properties of anaplastic astrocytomas, as well as the survival of patients with this disease.