The three characteristics that form the basis for the TNM staging system of CRC include3,8:
- The degree of penetration of the tumor (T) through the bowel wall.
- The presence or absence of nodal (N) involvement.
- The presence or absence of distant metastases (M).
Definitions for T, N, M Classification
Allele loss at or mutation of DCC, TP53, and KRAS are all associated with a poorer prognosis and these abnormalities are not common in tumors with MSI.9 Lymphovascular invasion on pathology of the primary tumor, as well as elevated carcinoembryonic antigen (CEA), have a negative prognostic implication as well.10
CRC molecular subtypes represent biologically and clinically distinct subgroups.11
- Consensus molecular subtype (CMS) 1: Hypermutated due to defective DNA mismatch repair with MSI and MLH1 silencing.
- CMS2: Predominantly displayed epithelial signatures with prominent WNT and MYC signaling activation.
- CMS3: Predominantly epithelial gene expression signatures and evidence of metabolic dysregulation in several pathways.
- CMS4: Increased expression of epithelial-mesenchymal transition (EMT) genes and evidence of prominent transforming growth factor-β activation.
- Samples with mixed features possibly represent either a transition phenotype or intratumoral heterogeneity.