Colorectal cancer is highly metastatic even when the tumors are small. To disseminate, cells use a complex and multistage process known as the epithelial-mesenchymal transition, in which epithelial phenotype is transformed into mesenchymal phenotype. The objective of this study is to describe the epithelial-mesenchymal transition in terms of gene expression profile and somatic alterations in samples of colorectal cancer with or without peritoneal carcinomatosis. We analyzed samples taken from 38 patients with colorectal cancer (stages II-IV) and samples from 20 patients with colorectal cancer complicated by peritoneal carcinomatosis. The expression ofZEB1, ZEB2, CDH1, VIM, andSNAI1was analyzed by real-time PCR.KRAS/BRAFmutations were mapped using sequencing. Microsatellite instability was evaluated by fragment analysis. Epithelial-mesenchymal transition was detected in 6 out of 38 samples of colorectal cancer (stages II-IV), 7 out of 20 tumors from patients with peritoneal carcinomatosis, and 19 out of 20 samples taken from carcinomatous nodules. Tumors of the mesenchymal subtype displayed high frequency of somatic mutations, microsatellite stability, and low degree of differentiation. The identification of epithelial-mesenchymal transition may be used as a marker of high metastatic potential, which is particularly relevant at early stages of tumor growth.

The primary structure of the APC gene DNA was examined in 108 patients younger than 45 years old diagnosed with “familial adenomatous polyposis, classic form” using PCR, conformation-sensitive electrophoresis, and Sanger sequencing. Mutations in the APC gene were observed in 78 patients; de novo mutations were observed in 17 cases. In the majority of cases (n = 45), patients exhibited frameshift mutations, 28 patients had nonsense mutations, and other 5 patients showed splicing mutations. We also revealed recurring variants: p.Arg232X (2 cases), p.Asp849GlufsX11 (2), p.Ser1068GlyfsX57 (2), p.Arg216X (3), p.Gln1062X (5), p.Arg213X (5), and p.Glu1309AspfsX4 (16). It was shown that, compared with other pathogenic variants in the APC gene in Russian patients, mutation p.Glu1309AspfsX4 does not result in earlier development of colorectal cancer and polyps. Nineteen mutations were described for the first time. The identified mutations were located between codons 142 and 1492 of the APC gene. This indicates the importance of investigation of all the gene coding exons. Pathogenic variants were observed in 16 of 35 studied relatives of the mutation carriers. All 16 relatives were included in the “risk group” for lifelong clinical monitoring.

Peutz-Jeghers syndrome (PJS) is an extremely rare autosomal dominant hereditary disease characterized by the growth of hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmented macules and an increased risk of malignant neoplasms of various localizations. In most cases the development of PJS is associated with the presence of a mutation in the STK11 gene, but not all patients have this mutation. This review presents the historical aspects of the first data on PJS, considers the clinical manifestations of the disease, current diagnostic methods, as well as recent knowledge about the genetic causes, about the risk of malignant neoplasms in patients with PJS, existing guidelines for screening and treatment of patients with PJS. However, the presence of a number of unresolved issues in genetics, monitoring and treatment indicates the need for further research.

Aim. In this research, we aim to develop a criterion for differentiating MutYH-associated polyposis from sporadic colon polyps.Materials and methods. A search for mutations in the MutYH gene was carried out using the PCR, electrophoresis and direct sequencing methods among the following groups of people: 18 patients under 45 years old with more than 100 polyps diagnosed in the large intestine; 86 patients over 45 years old with 4–100 polyps; 150 people of the control group.Results. Mutations in the MutYH gene were detected in 2 out of 18 patients having more than 100 polyps. Among 86 patients with 4–100 polyps, mutations were found in 10 people having more than 20 polyps. Mutations in the MutYH gene were not detected in patients with 4–19 polyps (p <0.05). The pathogenic significance of the disease development was established not only for biallelic, but also for monoallelic mutations.Conclusion. For the first time, the lower limit of the polyp number has been established, allowing the MutYH-associated polyposis to be differentiated from sporadic polyps.

MutYH-associated polyposis is the only polyposis syndrome with an autosomal recessive type of inheritance, often phenotypically similar to a weakened form of familial adenomatous polyposis. For the development of the disease mutations in both alleles of the gene are required, but an increased risk of developing colorectal cancer in carriers of monoallelic mutations is noted. The diagnosis of MutYH-associated polyposis should be suspected in a patient with colorectal cancer over 45 years old on the background of polyps in the colon. The review presents modern algorithms for diagnostic and treatment of the disease. Keywords: MutYH-associated polyposis, familial adenomatous polyposis, biallelic mutation, monoallelic mutation, colectomy

Background. PeutzJeghers 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. Aim. To assess the clinical picture and treatment of Russian patients with PJS. Materials and methods. A retrospective analysis of 30 patients from 25 families with an established diagnosis of PJS who were in the Ryzikh State Scientific Center for Coloproctology from 2011 to 2021 was carried out. All patients underwent instrumental examination, including esophagogastroduodenoscopy, colonoscopy, X-ray examination of the small intestine/CT-enterography, in the absence of invaginates video capsule endoscopy, as well as molecular genetic examination for the presence of pathogenic variants in the STK11 gene. All removed polyps were subjected to the histological examination. Results. The analysis of the clinical picture allowed us to establish the following data: the first complaints in patients were noted in childhood and adolescence, while the median age was 11 [7; 19] (0.524) years; pathogenic variants in the STK11 gene were identified in 26 (87%) cases, among which 10 were described for the first time; during the initial examination, polyps in the small intestine were detected in all 30 (100%) patients, in the stomach in 23/30 (77%) patients, and in the colon in 21/30 (70%); with an age, an increase in the number of polyps in all parts of the gastrointestinal tract was noted; before the diagnosis operations were performed urgently for intestinal obstruction; after the diagnosis of PJS, when polyps were detected in the gastrointestinal tract, endoscopic polypectomies were performed; if endoscopic removal of hamartomatous polyps was impossible, patients were operated as planned; malignant diseases of the predominantly reproductive system were detected in 8/30 (27%) patients. The median age of cancer detection was 52 [31; 52] (1759) years. Conclusion. Russian patients with PJS have population-specific features in the clinical picture of the course of the disease, which dictates the need to develop their own recommendations for monitoring and treatment of such patients.