KRAS, NRAS, BRAF mutations are associated with an unfavorable prognosis for colorectal cancer (CRC). At the same time, there is no single point of view on disease development during adjuvant chemotherapy (ACT). Objective. The authors aimed at studying KRAS, NRAS and BRAF mutations in the tumor and their influence on the clinical characteristics of colorectal cancer development. Materials and Methods. Paraffin blocks of the primary CRC tumor (n=37) were used as the material for the study. Using genomic DNA, isolated from the primary tumor, real-time PCR was used to determine the most common mutations in CRC: KRAS gene (exon 2, codon region 12–13), NRAS gene (exon 3, codon region 61), B6F V600E gene. Results. The results of genotyping of DNA samples isolated from the primary CRC tumor paraffin blocks showed that BRAF gene mutations were detected in 8.2 % of cases, NRAS gene mutations were detected in 5.4 % of cases, and KRAS gene mutations were detected in 37.8 % of cases. The authors didn’t reveal any dependencies of the mutation distribution on patients’ gender and age. The examined mutations were more common in adenocarcinomas of high and moderate degrees of differentiation. The relapse-free period after ACT in patients with identified KRAS, NRAS, BRAF gene mutations is significantly less than in those without mutations. Conclusion. The findings suggest that EGFR signaling pathway mutations (KRAS, NRAS and BRAF) increase the risk of disease recurrence and are an unfavorable prognostic factor. Keywords: colorectal cancer, NRAS, KRAS, BRAF mutations, adjuvant chemotherapy.

Introduction: The article covers issues related to modern methods of treatment of non-small cell lung cancer (NSCLC) with multiple synchronous metastases in brain, liver, mediastinal lymph nodes, skeletal bones and describes a clinical case of modern effective treatment and long-term follow-up of a patient with advanced NSCLC and extra- and intracranial metastatic spread. Purpose: Evaluation of modern methods of special antitumor treatment and their application in clinical practice for the treatment of metastatic NSCLC. Material and methods: Modern methods of proton and photon radiation therapy, targeted therapy are considered. Results: The use of modern methods of special antitumor therapy has increased the overall and relapse-free survival rate of patients with multiple metastases of NSCLC in brain, liver, mediastinal lymph nodes, skeletal bones reducing the need for additional interventions. This is confirmed by a long-term follow-up after modern effective antitumor treatment of a patient with advanced NSCLC and synchronous progression in the form of extra- and intracranial metastatic spread. The patient has been alive for more than 2 years from the moment of progression with an estimated life expectancy of 4–5 months. Conclusion: Modern methods of special antitumor therapy can increase the survival rate of patients with multiple synchronous NSCLC metastases in brain, liver, mediastinal lymph nodes, skeletal bones without significant deterioration in their quality of life.

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Aim: to analyze the structure and changes of colorectal cancer (CRC) epidemiology in the Ulyanovsk region in 2005–2019 according to the regional cancer register.Materials and methods: the study is based on statistical data on the primary detection of CRC in the districts of the Ulyanovsk region (form No. 7) in 2005–2019. Standardized rates of morbidity and mortality were evaluated. Data on the number, gender and age of the regional population were obtained in Ulyanovsk State Statistics Service.Results: the incidence of CRC in the region increased by 1.51 times over the analyzed period (from 31.12 to 49.58 per 100 thousand people). From the total number of newly diagnosed CRC in 2019, the urban population was 25%, and the rural population — 75%. The incidence rates in the districts of the region were assessed. The highest morbidity in males was detected at the age of 60–64 years old, and it was 1.58 times higher than in females. In the adult population under 30 years old, only few cases of colorectal cancer were detected. The main histological type of tumors was adenocarcinoma. Poorly differentiated tumors accounted for about 3%. The highest age-standardized rates for rectal tumors were 10.1 and 12.8 per 100 thousand people in 2005 and 2019, respectively; for the recto sigmoid tumors — 0.9 and 2.3 per 100 thousand people; and for the anal cancer — 0.4 cases per 100 thousand people in 2019. The male/female ratio of deaths from CRC in 2019 was 1.005:1.000.Conclusion: there has been a trend to an increase in the incidence of colorectal cancer among the Ulyanovsk region population in the period from 2005 to 2019. We identified some areas of the region that significantly differ in the incidence of colorectal cancer.

The prognostic factors that determine colorectal cancer (CRC) treatment are disease status, tumor grade, microsatellite instability, invasion degree, and the index of proliferative activity. However, the assessment of the adjuvant chemotherapy in colorectal cancer does not imply the assessment of angiogenic factors in a primary tumor. The aim of the paper is to evaluate the prognostic role of PDGFAA and VEGFA expression in tumor tissue of stages II/III colorectal cancers. Materials and Methods. Paraffin blocks of primary CRC tumor (n=50) were used as study material. Immunohistochemistry (IHC) was used to examine the expression of vasculoendothelial and platelet growth factors and calculate IHC score in the tumor parenchyma and CRC stroma. Results. According to IHC staining, CRC tumor expresses VEGFA and PDGFAA factors in 92 % of cases, in the resection line – in 37 % of the samples. There were no differences in VEGFA and PDGFAA expression in tumor parenchyma in CRC, depending on the process stage and grade degree. The cumulative risk of disease progression within a year after surgery in patients with stage II/III CRC with VEGFA+PDGFAA overexpression in the primary tumor is 4.9 times higher (CI 2.123–11.089, p=0.011) compared to the group of patients with reduced expression of the studied angiogenic factors. Conclusions. The data obtained suggest that co-expression of angiogenic VEGFA and PDGFAA factors in the tumor may reflect the initial CRC regarding neoangiogenesis. If VEGFA and/or PDGFAA IHC score is more or equal to 6, the risk of disease recurrence within 1 year from the start of medical observation increases, which is an unfavorable prognostic factor. Keywords: colorectal cancer, vasculoendothelial growth factor, platelet growth factor, adjuvant chemotherapy. Прогностическими факторами, определяющими тактику лечения при колоректальном раке (КРР), являются стадия заболевания, степень дифференцировки опухоли, микросателлитная нестабильность, степень инвазии, индекс пролиферативной активности. При этом оценка эффективности адъюватной химиотерапии при КРР не предполагает оценку ангиогенных факторов в первичной опухоли. Цель работы – оценить прогностическую роль экспрессии PDGFAA и VEGFA в опухолевой ткани на II–III стадиях колоректального рака. Материалы и методы. В качестве материала для исследования использованы парафиновые блоки первичной опухоли КРР (n=50). С помощью метода ИГХ исследована экспрессия васкулоэндотелиального и тромбоцитарного факторов роста путем расчета ИГХ-балла в опухолевой паренхиме и строме КРР. Результаты. По результатам ИГХ-окрашивания опухоль КРР экспрессирует факторы VEGFA и PDGFAA в 92 % случаев, в линии резекции – в 37 % образцов. Отличий в экспрессии VEGFA и PDGFAA в опухолевой паренхиме при КРР в зависимости от стадии процесса, степени дифференцировки выявлено не было. Кумулятивный риск прогрессирования заболевания в течение года после операции у больных с КРР II–III стадий при гиперэкспрессии VEGFA+PDGFAA в первичной опухоли выше в 4,9 раза (ДИ 2,123–11,089, р=0,011) по сравнению с группой пациентов со сниженной продукцией изученных ангиогенных факторов. Выводы. Полученные данные позволяют предполагать, что коэкспрессия ангиогенных факторов VEGFA и PDGFAA в опухоли может отражать исходный профиль КРР в отношении неоангиогенеза. При ИГХ-балле VEGFA и/или PDGFAA выше или равном 6 возрастает риск рецидива заболевания в течение 1 года от момента начала наблюдения, что является неблагоприятным прогностическим фактором. Ключевые слова: колоректальный рак, васкулоэндотелиальный фактор роста, тромбоцитарный фактор роста, адъювантная химиотерапия.