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.

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.

Introduction. mBRAF mCRC has the aggressive phenotype. The incidence of such mutation in Europe and the USA is around 8–14%, in Asian countries – 4–8%. The purpose of this population-based study was to determine the incidence and identifying prognostic factors in pts with mBRAF mCRC in Russia. Materials and methods. A multicenter retrospective analysis of clinical data and treatment results of pts with mBRAF mCRC was performed. The main method for determining mutations was a PCR. The main efficacy endpoint was progression free survival (PFS) at the 1 st line. Multivariate analysis was performed using Cox regression model. Results and discussion. 437 out of 8648 pts (5.17%) with a known mutational status had mBRAF (V600). Clinical data were collected from 131/437 (30%): the right-sided primary tumor – in 58,6%, left-sided – in 19%, rectum – in 21,4%. ORR in pts with mBRAF was 31%, median PFS was 6 months. We didn’t revealed any differences between FOLFOXIRI and doublets (XELOX/FOLFOX or XELIRI/FOLFIRI) in terms of PFS (HR 0.9, 95% CI 0.49–1.52, р = 0.6) and OS (HR 1.5, 95% CI 0.61–4.1, р = 0.35) in pts with mBRAF. Conclusions. The incidence of mBRAF gene in the population of pts with mCRC in the Russia is low and we found a high incidence of localization of the primary tumor in the rectum. We didn’t reveal any differences between the usual duplets and standard regimen for such mutation - FOLFOXIRI in term of 1 st line PFS.

Purpose: to evaluate the effect of somatic mutations of the KRAS, NRAS, BRAF genes and the status of microsatellite instability on the overall and disease-free survival of patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.Material and Methods. From 2012 to 2018, the study included 45 patients who underwent surgery for synchronous peritoneal carcinomatosis with colorectal cancer. In all patients, mutations of the KRAS, NRAS, BRAF genes and MSI status of the tumor and peritoneum metastases were determined using Sanger sequencing, fragment analysis and digital droplet polymerase chain reaction. The effect of mutations on patient survival was evaluated.Results. The prevalence of somatic mutations was 69 % of patients. The discordance between the tumor and peritoneum metastases was 9 %. All tumors and peritoneum metastases were microsatellite stable. KRAS, NRAS, BRAF mutations did not affect the overall and disease-free survival (p=0.87 and p=0.85, respectively).Conclusion. Somatic mutations in the KRAS, NRAS, or BRAF genes are not a prognostic factor affecting the overall and relapse-free survival of colorectal cancer patients with peritoneal carcinomatosis. The molecular status of primary tumor may differ from the status of peritoneal metastasis. It should be taken into account when prescribing targeted drugs.

The aim of this study was to determine the characteristics of Russian patients with microsatellite instability (MSI) tumors. MSI in the tumor was determined in 514 patients with colon cancer using PCR and subsequent fragment analysis for five markers (NR21, NR24, BAT25, BAT26, and NR27). In the presence of microsatellite instability, the mismatch repair (MMR) system genes were examined using the NGS and MLPA methods to establish the diagnosis of Lynch syndrome. The overall frequency of MSI tumors was 15%: at stage I—19% (9/48), at stage II—21% (44/213), at stage III—16% (26/160), and at stage IV—2% (2/93). Patients with MSI tumors differed in the age of diagnosis, tumor localization, time of cancer recurrence, and stage of the disease. The overall and disease-free survival of patients whose tumors had MSI status was higher than that of patients with microsatellite-stable status, p = 0.04 and p = 0.02, respectively. Analysis of overall and disease-free survival of patients with Lynch syndrome and patients with sporadic colon cancer, but with MSI status, did not reveal significant differences, p = 0.52 and p = 0.24, respectively. The age of patients with Lynch syndrome was significantly younger than that of patients with sporadic colon cancer whose tumors had MSI status (p < 0.001).