that they promote tumorigenesis and tumor progression. The most common driver mutations in CRC have been described in a series of publications and include mutations in APC, TP53, KRAS, and PIK3CA [9, 11]. For example, APC is the most commonly mutated gene in CRC (72% mutation rate in The Cancer Genome Atlas) and is important as an early driver of adenoma formation. The APC protein acts as a tumor suppressor. Alteration in APC causes accu­mulation of beta- catenin which translocates to the nucleus and binds to LEF and TCF, causing transcription upregulat­ing multiple pathways. In addition, loss or mutation of APC can lead to transcriptional activation independent of ß-catenin. TP53 mutation is the second most common alter­ation in CRC.It is more commonly altered in patients with more advanced disease and is considered a late driver. It is a tumor suppressor gene because its normal function is to cause damaged cells to stop dividing until the DNA can be repaired and to undergo apoptosis if the DNA cannot be repaired. Mutation or loss of TP53 results in increased pro­liferation, decreased DNA repair, and decreased apoptosis. Mutations of clinical relevance include RAS mutations which occur in about half of patients with CRC including KRAS and NRAS. These are important because patients with RAS mutations do not benet from treatment with anti-epi­dermal growth factor receptor (EGFR) agents [12]. Additionally, around 10% of patients have tumors contain­ing mutations in BRAF, which is important because this is a biomarker of worse survival in stage 4 patients [13]. Although BRAF inhibitors can improve outcome in other tumor types with these mutations, in 95% of CRCs are resis­tant to BRAF inhibition via redundant alterations in the MAPK pathway [14]. Another key pathway in CRC that is especially important in metastasis is the epithelial- to­mesenchymal transition (EMT). [15] EMT is the process whereby epithelial cells acquire mesenchymal properties. This allows the cells to change their architecture, interact differently with their microenvironment, and become inva­sive. Proteins important in EMT in CRC are ZEB1 and ZEB2, TGF-β, SNAIL, and vimentin. EMT and ZEB2 spe­cically have such an important role in metastasis that small trials have shown that addition of nuclear ZEB2 staining in CRC to the staging system will improve patient stratica­tion for prediction of outcome [16].