Molecular pathology of colorectal cancer

Abstract

Colorectal cancer (CRC) is a molecularly heterogeneous disease arising from gradual accumulation of genetic and epigenetic changes. In the last decade, great efforts have been made to classify CRC according to molecular features. This has led to several proposals of molecular subtyping. Recently, consensus molecular subtypes (CMS) have been proposed based on the integration of previously existing categorizations and additional comprehensive molecular studies. Microsatellite instability (MSI) is a highly specific molecular feature in CRC with a therapeutic impact, for example for immunotherapy. MSI is recognized as a separate CMS subtype. Beyond MSI, molecular subtyping may also be helpful for further differentiating CRC into prognostically distinct groups and for identifying new treatment targets, particularly for CMS with more aggressive behavior and resistance to conventional systemic treatment. Molecular subtypes may also exhibit distinctive morphological features, which may open the horizon for morphomolecular diagnostics based on digital pathology and machine learning. This review article summarizes current aspects of the molecular pathology of CRC with a focus on molecular subtyping in the context of pathological features and therapeutic applications.