Abstract
This review reveals the anatomical, physiological and embryogenetic features of the proximal colon to explain the reasons for such frequent localization of mucinous phenotype of adenocarcinoma (MAC) here. It was shown that later differentiation in embryogenesis causes relative insufficiency of the proximal part as a structure of the digestive and immune systems. Physiologically lower lymphoid tissue (GALT) density here leads to the formation of a certain composition of the intestinal microbiota, which is different from that in the distal part, which is a significant link in the etiopathogenesis of proximal colon cancer. It is confirmed also by different composition of biofilms on the surface of epithelial tumors in the right and left halves of the colon, as well as differences in the molecular mechanisms of carcinogenesis, depending on the location of the cancer. Common for proximal part genetic changes, called as CIMP-phenotype, microsatellite instability and BRAF proto-oncogene mutation lead to excessive secretion of specific mucin fractions (mainly MUC2 and MUC5AC), the imbalance of its composition and the formation of MAC. An earlier age of onset, frequent association with hereditary non-polypous colorectal carcinoma, the predominance of MUC2 and MUC5AC fractions, similar to the embryonic period, as well as a higher level of cancer-embryonic antigen in patients with MAC indicate the influence of anatomical, physiological and embryogenetic features of the proximal colon on carcinogenesis long before its formation. Thus, a detailed understanding of MAC carcinogenesis is necessary for an adequate assessment of its effective prevention in time, as well as dealing with it as with specific nosological unit requiring specific treatment principles.
Highlights
This review reveals the anatomical, physiological and embryogenetic features of the proximal colon to explain the reasons for such frequent localization of mucinous phenotype of adenocarcinoma (MAC) here
Lower lymphoid tissue (GALT) density here leads to the formation of a certain composition of the intestinal microbiota, which is different from that in the distal part, which is a sig nificant link in the etiopathogenesis of proximal colon cancer
A detailed understanding of MAC carcinogenesis is necessary for an adequate assessment of its effective prevention in time, as well as dealing with it as with specific nosological unit requiring specific treatment principles
Summary
Физиологически более низкая плотность лимфоидной ткани (GALT) здесь приводит к формированию определенного состава кишечной микробиоты, отличного от такового в дистальном отделе, что является значимым звеном в этиопатогенезе злокачественных новообразований проксимального отдела толстой кишки. Характерные для проксимального отдела изменения в виде CIMP-фенотипа, микросателлитной нестабильности и мутаций протоонкогена BRAF приводят к избыточной секреции отдельных фракций муцина (преимущественно MUC2 и MUC5AC), дисбалансу его состава и формированию МАК.
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