HISTOPATHOLOGICAL AND MOLECULAR CHARACTERISTICS OF COLORECTAL CANCER – REVIEW OF THE SIGNIFICANCE OF THE EPITHELIAL-MESENHYMAL TRANSITION
Abstract
Colorectal cancer (CRC) is the third most frequently diagnosed cancer and the second
most common cause of death among malignant neoplasms, including both sexes. The most
important prognostic and predictive factors for CRC are the histological type and grade of the
tumor, TNM stage of the tumor disease, lympho-vascular and perineural infiltration, tumor
budding and residual status. The molecular classification of CRC is based on its genetic
characteristics, cellular specifications, cancer microenvironment and immunological
characteristics, and is of great practical importance, as individual subtypes differ in their
clinical course and respond differently to chemotherapeutic and biological treatment.
Epithelial-mesenchymal transition (EMT) is a transdifferentiation process in which epithelial
cells acquire properties that are characteristic of mesenchymal cells. During neoplastic
progression, cancer cells acquire genetic and epigenetic features that affect oncogenic and
tumor suppressor genes, which ultimately results in the activation of the type III EMT
programme, giving them the potential to invade and metastasize, contributing to the stemness
of cancer cells, their resistance to drugs and immune response avoidance. Changes made in
cells, during EMT, can be reversible upon arrival at a suitable location for colonization, by a
process opposite to EMT, called mesenchymal-epithelial transition (MET), during which cells
regain characteristics of the epithelial phenotype. In most human cancer types, a complete shift
from an epithelial to a mesenchymal phenotype during EMT is rarely encountered, but most
cancers show partial EMT. Cells undergoing partial EMT are difficult to identify, due to their
phenotypic heterogeneity and variable expression of EMT markers. It is necessary to find new
biomarkers of EMT, especiallypartial EMT, as well as a better understanding of the relationship
between EMT and resistance to therapy, in order to develop new therapeutic approaches for
CRC.
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