Wild-type KRAS acts as a switch during signal transduction; however, somatic mutations that activate regulators and effectors of Ras proteins are common in tumor development and cancer [1, 2, 3]. In approximately 35%-42% of early colorectal cancer (CRC) patients, the KRAS mutation inhibits KRAS GTPase, resulting in a constitutive KRAS activation and, thus, activating a Ras/Raf signaling pathway. In CRC, 97% of KRAS mutations occur in codons 12 and 13 of exon 2, and more than 97% of changes in the protein are attributable to changes in the amino acid sequence by the substitution of seven DNA base pairs [4]. BRAF is a human gene that encodes the protein B-Raf, which is considered a proto-oncogene, encoding a serine/threonine protein kinase [5]. B-Raf is a member of the Raf kinase family that regulates the Ras/Raf/MEK/extracellular signal regulated kinase (ERK) pathway and is involved in division, differentiation, and secretion [6]. The most common BRAF mutation is a missense mutation (V600E, formally known as V599E), resulting in glutamic acid in place of valine that generates an abnormality in the MEK/ERK signaling pathway in CRC [7].

The mitogen-activated protein kinase (MAPK)/ERK signaling pathway is a highly conserved intercellular signaling system present in multicellular organisms and plays an essential role in cancer progression. MAPK/ERK activation is a common feature of tumors with KRAS, NRAS, or BRAF mutations [8, 9]. A highly activated MAPK/ERK pathway is found in approximately 30% of cancers and over 60% of melanomas, and it is associated with tumor proliferation and migration. BRAF is upstream of the MAPK/ERK pathway, and a single amino acid change, resulting in a valine-toglutamyl acid substitution at position 600 (V600E), accounts for ~90% of BRAF mutations. ERK1/2 are important kinases in the MAPK pathway. Therefore, activation of ERK1/2 could be considered as a target factor related with CRC carcinogenesis through the serrated pathway [8].

The authors of this study investigated the clinicopathologic outcomes of BRAF mutation and ERK1/2 expression in patients with CRC and the possibility of their use as prognostic indicators. The authors found that BRAF mutation and ERK1/2 expression might be associated with advanced or more aggressive CRC [10].