Lynch syndrome is the most common cancer-prone syndrome associated with a high risk of colorectal cancer (CRC), neoplasms of the upper gastrointestinal system, the urinary tract, the female reproductive system, brain tumours and others. The only known form of hereditary endometrial cancer is also diagnosed as part of Lynch syndrome. One or more pathogenic germline mutations in one of the mismatch repair (MMR) genes are the cause of Lynch syndrome. Mapping of MMR genes and the discovery of microsatellite instability (MSI) have given rise to the possibility of using these clue characteristics of the pathogenic process for the elaboration of a screening test for Lynch syndrome. Being highly accurate and superior to all previously developed clinical criteria and guidelines, MSI-testing along with the assessment of the expression patterns of MMR proteins by immunohistochemistry has taken the leading role in the early diagnosis of Lynch syndrome. This article focuses on a brief review about the main evolutionary stages of clinical, anamnestic, molecular and genetic criteria for Lynch syndrome together with the results of our own research on the accuracy of the Amsterdam criteria, the Bethesda guidelines and MSI-diagnostics in the determination of the indications for MMR-genotyping in colorectal cancer patients suspected for Lynch syndrome.

Background. According to the literature, BRCA1-associated breast cancer (BC) most often belongs to the triple negative (TNBC) molecular subtype. The data on the contribution of other molecular subtypes to this group of patients differ among different studies.The study objective is to evaluate the frequency of different tumor molecular subtypes in BC patients with BRCA1 gene mutation treated in N. N. Blokhin National Medical Research Center of Oncology in the period from 2017 to 2020.Materials and methods. The study included BC patients with a mutation in the BRCA1 gene (n = 209) identified as a result BRCA1 mutation screening of patients with BC. DNA diagnostics was carried out on blood samples of patients using the real-time polymerase chain reaction method. After analyzing the patients primary documentation clinical and morphological data were taken into account: the age of diagnosis, the stage of the disease, the results of immunohistochemical studies (estrogen receptor status, progesterone receptor status, HER2 expression, Ki-67 proliferation index). The assignment to the particular molecular tumour subtypes was performed according to estrogen receptor status, progesterone receptor status, HER2 status and Ki67 value.Results. Clinical and pathomorphological data of 209 patients with BRCA1-associated BC were analyzed. The age at diagnosis ranged from 23 to 72 years, the median age was 40 years, the mean age was 41.46 ± 9.82 years. BC associated with BRCA1 was found to be TNBC in 71.3 % and luminal B, HER2 negative (LumB–) in 19.1 % of the cases. Other tumour subtypes were much less common: luminal B, HER2 positive (LumB+) in 7.2 %, luminal A (LumA) in 1 % and HER2-positive (HER2+) in 1.4 % of the cases. The frequency of subtypes was estimated in different age groups (1st – patients 23–34 (n = 53), 2nd – 35–49 (n = 111), and 3rd – 50–72 (n = 45) years old). TNBC frequency was 81.1 % in the 1st group, 73.9 % in the 2nd and 53.4 % in the 3rd group; LumB– frequency was 15.1, 15.3 and 33.3 % respectively. Using the Fisher test it was shown that the differences in frequencies were statistically significant between groups 1st and 3 rd, as well as between groups 2 nd and 3 rd (p <0.05).Conclusion. TNBC was the main molecular subtype in all age groups of BC patients with BRCA1 germinal mutation, TNBC frequency was lower in the older age group. LumB– subtype was also common in BRCA1-associated tumors especially in older women.

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Background. The study aims to compare the functional outcomes and quality of life in patients having variant rectal reconstruction procedures after low anterior resection for cancer.Materials and methods. A prospective randomised controlled trial enrolled 90 patients who underwent total mesorectumectomy with formation of J-pouch (J-P), side-to-end (STE) or end-to-end (ETE) anastomoses.Results and discussion. We analysed 22 J-P, 30 STE and 38 ETE patients. For technical reasons, 26.6 % J-Ps were remodelled to other anastomoses. The neorectal sensory threshold, first and permanent defecation urges and maximal tolerated volume were higher in J-P at months 3–6–12 postoperatively.Severe low anterior resection syndrome events at post-surgery month 6 were significantly more frequent in the ETE vs. J-P and STE cohorts (21, 0 and 3.3 %, respectively, p < 0.05). Stool frequency was significantly lower in J-P vs. STE and ETE at months 3–6–12. Wexner score was 3, 5, 6 at month 6 (p < 0.05) and 0, 1, 1 at month 12 for J-P, STE and ETE, respectively (p > 0.05). Evacuatory dysfunction was present at month 6 in 59.1 J-P, 33.3 STE and 21.1 % ETE.Quality of life (FIQL) in J-P and STE was significantly higher vs. ETE anastomoses in the Lifestyle (3.21, 3.22 and 3.03, respectively, p < 0.05) and Coping (3.29, 3.21 and 2.95, respectively, p < 0.05) scales to month 12 postoperatively.Conclusion. The J-pouch formation after low anterior resection ameliorates anal continence at months 3–6 post-surgery, reduces low anterior resection syndrome and improves quality of life (FIQL). The ease of implementation and irrelevance of evacuatory dysfunction in side-to-end anastomosis make it a superior choice over end-to-end surgery.

Настоящее учебно-методическое пособие посвящено практическим аспектам генетической диагностики синдрома Хиппеля-Линдау и составлено в соответствии с ФГОС ВО по специальностям 31.08.30 «генетика», 31.08.06 «лабораторная генетика», 31.08.57 «онкология», 31.08.68 «урология», 31.08.53 «эндокринология», 31.08.42 «неврология», 31.08.05 «клиническая лабораторная диагностика» и рабочими программами кафедры онкогенетики ИВиДПО ФГБНУ «МГНЦ». Пособие предназначено для ординаторов по указанным выше специальностям, аспирантов по научным специальностям 1.5.7. «генетика», 3.1.6. «онкология, лучевая терапия», 3.3.8. «клиническая лабораторная диагностика», 3.1.13. «урология и андрология», 3.1.19. «эндокринология» и 3.1.24. «неврология», а также для врачей-генетиков, врачей-онкологов, врачей-урологов, врачей-эндокринологов, врачей-неврологов, врачей – лабораторных генетиков и специалистов в области клинической лабораторной диагностики при обучении их по программам повышения квалификации. Печатается по решению учебно-методической комиссии Института высшего и дополнительного профессионального образования ФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова от 30 сентября 2021 г.