The thesis is devoted to the improvement of the pathomorphological diagnosis of colon polyps with the definition of optimal diagnostic morphological criteria to predict their course. The solution to the problem and the substantiation of the obtained results was achieved due to a set of modern diagnostic techniques of polypoid lesions of the colon: histological, histochemical, immunohistochemical and statistical processing of digital data. To achieve the aim and solve the tasks set in the thesis, the following studies were conducted: a retrospective analysis of archive biopsy materials for the period of 2005-2016 to determine the rate, structure, sex-age, and morphological features of polypoid lesions of the colon and a prospective study of pathomorphological and immunohistochemical features of cases of newly diagnosed polypoid neoplasms of the colon with an asymptomatic course on the current materials of 200 autopsies, conducted on the basis of the Communal Facility of Lviv Regional Council "Lviv Pathology Bureau". The results of the prospective study revealed that hyperplastic polyps with asymptomatic course compared with conventional hyperplastic polyps in the study of archive biopsy materials were more often located in the proximal areas of the colon, characterized by the spread of serration to a considerable depth of crypts, partially including basal divisions, but not at all depth, deformation of crypts, pathological branching and dilation of basal areas, secretion of a significant amount of mucus. Some neoplasms had a topographical change in the proliferation of enterocytes with the shift in the surface areas of crypts, higher proliferative activity of enterocytes, and a greater ratio of the indexes of the upper and lower parts of the crypts Ki-67 accounting for 0.82±0.18, in comparison with the conventional polyps with Ki-67 = 0.27±0.08 and in individual cases, Ki-67=0.51±0.12 meaning a disturbance of the topography of the proliferative compartment. The study of microsatellite instability of hyperplastic polyps enabled to determine the absence in some cases of MSH2, MSH6, PMS2 and MLH1 protein expression, which validates the formulation of the concept of carcinogenesis of colorectal cancer associated with hyperplastic polyps and, accordingly, an adverse course of hyperplastic polyps. Except for hyperplastic polyps, manifestations of microsatellite instability were established to occur in the adenomas with low-grade dysplasia. In the group of adenomas with minimal dysplasia, the results of the immunohistochemical study of gene expression of the mismatch repair system of mismatched nucleotides demonstrated their decrease and polymorphism. In typing of MLH1 and PMS2, only 30 % of the epithelial cells of the structural elements were positive, whereas typing of MSH6 showed up to 60% of positive results and MSH2 - 100%. Thus, microsatellite instability and reduced gene expression of the mismatch repair system of mismatched nucleotides (MLH1 and MSH2) further determine the severity of the clinical course of adenomas with low-grade dysplasia and the adverse outcome. Evaluating the status of microsatellite instability and proliferative activity in the group of adenomas with high-grade dysplasia, we established the significant expression of genes of mismatch repair system of mismatched nucleotides, which explains the traditional way of carcinogenesis of colorectal cancer through the sequence of adenoma-adenocarcinoma (due to chromosomal instability and the accumulation of mutations in oncogenes and tumor suppressor genes) and is a conventional concept of colorectal cancer. It was determined that tubular adenomas mostly located in the distal colon and characterized by an average proliferative activity (Ki-67 from 33 to 44 %) were dominant in the group of adenomas with low-grade dysplasia. At the same time, the Ki-67 ratio in the upper and lower zones in tubular adenomas increases up to 1.4-2.1 in comparison with the proliferative activity of enterocytes in asymptomatic hyperplastic polyps, where the Ki-67 ratio was 0.82±0.18. The shift of the proliferation zone in the tubulovillous adenomas was even more pronounced, where the Ki-67 rate reached 2.49. The proliferative tumor cells were located predominantly in the villi, and the index of proliferative activity ranged from 40 % to 75 %, with an average value of 58.45 %. Ki-67 rate further increases and reaches 2.65 in adenomas with signs of high-grade dysplasia. The study of the functional capacity of goblet cells in adenomas with low-grade dysplasia showed accumulation of secretory products of intense blue (alcian blue) stain in cells with intact production of mucus, indicating an increase in the content of glycosaminoglycans in the mucin. However, it was investigated that goblet cells practically disappear in the adenomas with high-grade dysplasia; only occasionally they can be detected with alcian-blue stain. In the immunohistochemical study of proteins of the mismatch repair system for the detection of colorectal cancer with microsatellite instability, one adenocarcinoma of a moderate degree of differentiation (G2) was diagnosed in our materials, which accounted for 12.5 %, and is consistent with data in the literature. On the basis of modern morphological studies, it was first established that in the presence of defects in DNA repair proteins, hyperplastic polyps and adenomas with low-grade dysplasia are precursors to the development of colorectal cancer through microsatellite instability, while adenomas of high-grade dysplasia demonstrated sustained expression of MSH2, MSH6, PMS2, and MLH1 proteins. Adenomas with high-grade dysplasia become malignant through chromosomal instability. Based on the given study, for the first time, a hypothesis has been put forward that the maximum risk of microsatellite instability may occur in patients with hyperplastic polyps and adenomas with low-grade dysplasia. It has been shown for the first time that the tumor progression of adenomas with various degrees of dysplasia is not consistent and does not necessarily pass all stages of transition from low- to high-grade dysplasia and then to malignancy. The scientific data on distribution, localization and clinical morphological variants of polypoid lesions of the colon with the asymptomatic course in patients of any age and gender were supplemented. Based on the results of the study conducted, it was established that the immunohistochemical detection of the proteins in the DNA repair system together with the evaluation of the clinical and morphological features of the polypoid lesions of the colon enables to predict their course.
