In the thesis, in order to improve pathomorphological prognosis of adenomas and serrated lesions as well as the prognosis of colorectal cancer aggressiveness the following parameters were investigated: immunohistochemical parameters of proliferation and apoptosis (based on Ki-67, p53, caspase-3 expression), neoangiogenesis (based on VEGF-A, VEGFR-1, VEGFR-2, CD34 expression), stem cell markers expression (CD44, ALDH1, EpCAM) in colonic polyps biopsies and colorectal adenocarcinoma surgical material; immunohistochemical parameters of epithelial-mesenchymal transition (based on E-cadherin, β-catenin, СK-20, vimentin, α-SMA expression) and mucin phenotype (based on MUC1, MUC2, MUC4, MUC5AC, Cdx-2 expression) in colorectal adenocarcinoma surgical material; molecular-genetic parameters of Ki-67, TP53, KRAS, CDH1, CTNNB1 transcriptional activity in colorectal adenocarcinoma surgical material. Comparative analyzes of the data obtained for each histological type of colonic polyps with different degrees of dysplasia, for high-grade colonic polyps and well-differentiated colorectal adenocarcinoma, for each stage of colorectal adenocarcinoma progression, as well as for non-metastatic and metastatic carcinoma were carried out.
In the thesis, it was established that epithelial dysplasia with increased proliferation and apoptosis levels, as well as increased EpCAM expression and increased number of ALDH1+ epitheliocytes and stromal cells play a key role in the progression of conventional adenomas of the distal colon. Epithelial dysplasia with increased proliferation and apoptosis levels plays a key role in the progression of serrated lesions of the distal colon, augmented by the increased number of microvessels in hyperplastic polyps exclusively. It was shown that high-grade conventional adenomas of the distal colon differ from G1 colorectal adenocarcinoma by significantly lower р53, VEGF-A, СD44 expression indexes, as well as significantly lower ALDH1 expression by stromal cells; serrated lesions differ by significantly lower Ki-67, p53, VEGF-A, VEGFR-2 expression indexes, as well as significantly lower СD44 and ALDH1 expression by stromal cells.
During the colorectal adenocarcinoma progression from the Ist up to the IVth stage, transcriptional activities of KRAS and TP53 genes increase, whereas transcriptional activity of Ki-67 gene decreases, immunohistochemical р53 and Ki-67 expression indexes change accordingly. During the progression, transcriptional activity of CDH1 and E-cadherin expression level decrease, while transcriptional activity of CTNNB1 and β-catenin expression level keep elevated. At the same time, indicators of epithelial-mesenchymal transformation appear: CK-20 expression level decreases, vimentin and α-SMA expression levels increase. During the colorectal adenocarcinoma progression from the Ist up to the IInd stage, MUC1, VEGF-A, VEGFR-2, CD44 expression levels increase, as well as ALDH1 expression by stromal cells, whereas MUC2 and MUC4 expression levels decrease. The colorectal adenocarcinoma progression from the IInd up to the IIIrd stage differs by the elevation of Cdx-2 and EPCAM expression levels, while the progression from the IIIrd up to the IVth stage differs by the elevation of EPCAM expression level and ALDH1 expression level by both cancer сells and stromal cells. Metastatic colorectal adenocarcinoma differs from non-metastatic one by significantly higher mRNA KRAS, mRNA TP53 and р53, VEGF-A and VEGFR-2, vimentin,
α-SMA, MUC1, EpCAM, CD44 expression levels, as well as higher ALDH1 expression by stromal cells; and by significantly lower mRNA Ki-67 and Ki-67,
Е-cadherin and CK-20, MUC2 and MUC4 expression levels.
