About 7% of all cancer deaths are caused by pancreatic cancer (PCa). PCa is known for its lowest survival rates among all oncological diseases and heterogenic molecular profile. Enormous amount of genetic changes, including somatic mutations, exceeds the limits of routine clinical genetic laboratory tests and further stagnates the development of personalized treatments. We aimed to build a mutational landscape of PCa in the Russian population based on full exome next-generation sequencing (NGS) of the limited group of patients. Applying a machine learning model on full exome individual data we received personalized recommendations for targeted treatment options for each clinical case and summarized them in the unique therapeutic landscape.

The somatic mutation in BRAFT1799A (BRAFV600E), the data on the prognostic role of which are contradictory, is one of the most common molecular genetic abnormalities in the cells of papillary thyroid carcinoma (PTC).OBJECTIVE:To investigate the association of the immunoexpression of mutant BRAF in PTC with different morphological characteristics and long-term treatment results in patients.MATERIAL AND METHODS:Information on inpatients with PTC was obtained from the database of the Pathology Department, A.F. Tsyb Medical Radiology Research Center (a branch of the National Medical Radiology Research Center, Ministry of Health of the Russia). The paraffin-embedded blocks of surgically removed primary, metastatic, and recurrent PTC tissues were cut and stained with hematoxylin and eosin and anti-mutant BRAF monoclonal antibodies. The results of immunohistochemical tests were assessed and the frequency of BRAF immunoexpression was analyzed in relation to various clinical and morphological parameters of tumor growth, the pattern and volume of treatment in the patients, by taking into account its long-term results (the presence or absence of tumor recurrence and metastases in the postoperative period).RESULTS:The expression of mutant BRAF (BRAF+) was noted in 29 (39.3%) of the 74 cases of PTC. The BRAF+ group differed from the BRAF group by a higher proportion of male patients, older age, advanced clinical stage of carcinoma, a predominance of papillary structure of tumors, and a higher frequency of their recurrence and/or metastases in the postoperative period.CONCLUSION:The immunohistochemical assessment of BRAF status opens up a possibility to predict local recurrence and metastases in the postoperative period in patients treated for PTC.

45 Гастроинтестинальная стромальная опухоль (GIST) является редкой опухолью пищеварительной системы. Частота выявления GIST варьирует от 0,1 до 3% среди всех гастроинтестинальных злокачественных опухолей. В России ежегодно регистрируется 2000—2500 случаев GIST различной локализации. Одинаково часто болеют как мужчины, так и женщины. В 50% случаев GIST диагностируют на поздних стадиях развития в связи с отсутствием специфических симптомов и трудностью гистологической верификации опухоли. GIST относится к мезенхимальным опухолям. Развитие GIST происходит из клеток Кахаля, расположенных в интерстициальных нервных сплетениях и отвечающих за моторику ЖКТ. В большинстве случаев развитие GIST связано с мутациями протоонкогена с-KIT (70—85% мутаций), наиболее часто в экзонах 11 (75%), 9 (15%), 13 и 17 (2—5%) и в 5% случаев с мутацией в экзонах 18, 12 и 14 гена PDGFRα, кодирующего тирозинкиназный рецептор тромбоцитарного фактора роста [1—5]. В 10—15% встречается дикий тип GIST. Эти особенности необходимо учитывать при назначении ингибитора тирозинкиназ (иматиниба мезилат). Наиболее чувствительны к этому препарату опухоли с мутацией в экзонах 11 и 13 гена с-KIT, менее чувствительны при мутации в 9 экзоне гена с-KIT и нечувствительны при мутации в 18 экзоне гена PDGFRα. При диком типе GIST эффект от иматиниба мезилата наблюдается в 40% случаев (табл. 1) [1, 2, 6]. В подавляющем большинстве случаев GIST встречаются как солитарные опухоли различной локализации. GIST первично-множественной локализации встречается крайне редко (менее 1%) либо спорадически — как первично-множественная GIST без семейного опухолевого анамнеза, либо является проявлением наследственных синдромов. В зависимости от молекулярно-генетичеdoi: 10.17116/onkolog20176245-50

The paper analyzes the data available in the literature on the morphological and prognostic features of relatively rare high-grade thyroid cancer. It shows the difficulties and unsolved problems of morphological diagnosis and the possibilities of current methods for immunohistochemical and molecular genetic studies to determine the malignant potential of the tumor and prognosis.

The paper describes a rare case of concurrent two different histological (follicular and columnar cell) variants of papillary carcinoma in one thyroid with columnar cell metastases to the lymph nodes and femoral bone. There are morphological features of and differences in BRAF status in the cells of two variants of papillary thyroid carcinoma.

AIM To ascertain the role of high antibodies (Ab) titers to microsomal antigen (MA) of the thyroid in clinical manifestations of cytopenic syndromes. MATERIAL AND METHODS Clinical data are presented on 144 patients with depressed hemopoiesis having different levels of thyroid Aab. RESULTS When the titer was significantly elevated (41% patients with immune cytopenias), hematological malignancies run with recurrences, remission is rare. Treatment of the thyroid pathology improves hematological indices in some cases though does not reduce titers of Ab thyroid MA. CONCLUSION Detection of autoimmune pathology of the thyroid is necessary not only for specification of the concurrent process diagnosis but also for initiation of adequate combined treatment.

AIM To study the level of thyroid antibodies (TAB) in blood diseases. MATERIAL AND METHODS TAB levels dynamics was studied in 413 patients with hematological diseases. RESULTS Increased incidence of cases with high Ab titer to thyroid microsomal antigen was found. High and moderate titers were revealed in 33% of all examinees, including 41%, 22%, 32% and 29% among patients with immune cytopenia, chronic lymphoid leukemia, generalized mature-cell lymphoma and myeloproliferative diseases, respectively. These high and moderate titers were rather stable. In 15% patients Ab were elevated insignificantly, this rise being unstable. CONCLUSION Stable high titers of antibodies to thyroid antigens point to increased incidence rates of concomitant autoimmune hyroiditis in patients with blood diseases.

Aim. To study the level of thyroid antibodies (TAB) in blood diseases.Material and methods. TAB levels dynamics was studied in 413 patients with hematological diseases.Results. Increased incidence of cases with high Ab titer to thyroid microsomal antigen was found. High and moderate titers were revealed in 33% of all examinees, including 41%, 22%, 32% and 29% among patients with immune cytopenia, chronic lymphoid leukemia, generalized mature-cell lymphoma and myeloproliferative diseases, respectively. These high and moderate titers were rather stable. In 15% patients Ab were elevated insignificantly, this rise being unstable.Conclusion. Stable high titers of antibodies to thyroid antigens point to increased incidence rates of concomitant autoimmune hyroiditis in patients with blood diseases.

The effect of the synthetic peptide IEW (Neogen) with immunomodulating properties on postradiation recovery of haemopoiesis was investigated. We have shown that Neogen is a potential stimulator of haemopoiesis. The administration of Neogen after irradiation shortened duration of period of the recovery of the compartment of CFU-S-8 and the amount of bone marrow cells. The comparision of the effects of Neogen and GM-CSF (Leucomax) and G-CSF (Granocyte 34) have shown that the targets for these agents are probably different: polypotent CFU-S-for Neogen, and CFU-GM-for GM-CFS. Based on the results, we suggested the mechanism of Neogen effects on heamopoiesis.

It was studied on mice how prior whole body hyperthemia affects a colony-forming ability of bone marrow after gamma-irradiation. It was found that heating of the animals (42 degrees C, 10 min) 18-22 h before their total irradiation (4 Gy) increases 2-fold the level of CFUs8 and CFUs12 determined in the spleen exotest. The induced radioresistance correlated with accumulation of heat shock proteins, HSP70 and HSP25, in tissues of preheated mice. Injection of quercetin (a selective inhibitor of the heat shock protein synthesis) 0.5 h before the heating fully abolished both the subsequent heat shock protein accumulation and the rise in CFUs populations as compared with control. It is suggested that heat shock proteins, whose expression increases in response to hyperthermia, can play a role of endogenous radioprotectors. Possible mechanisms of their protective action under irradiation are discussed.

Th distribution of autoimmune thyroiditis in the patients with diseases of blood system was investigate. The attribute of autoimmune thyroiditis was revealed by the detection of antimicrosomal antibodies. It was established that the autoimmune thyroiditis are more often in patients with various hematological diseases than in control group. It is supposed that the increase in frequency of some hematological diseases in residents suffered from the Chernobyl accident can be defined not only by the influence of the radiation on blood system, but also can be connected with damage to thyroid glands.