BRAF-V600E mutation was significantly associated with proximal localisation (OR = 2.71; P < 0.00001) and CIMP-H status (OR = 4.81; P < 0.0001) in both SSA and TSA, with polyp size <10 mm (OR = 0.41; P = 0.02) in TSA, and with endoscopic pit pattern II-O (OR = 13.11; P < 0.00001) and expression of MUC5A5 (OR = 4.43; P = 0.003) and MUC6 (OR = 2.28; P < 0.05) in SSA.
The subgroup of colon cancer (CRC) characterized by mutation in the BRAF gene and high mutation rate in the genomic DNA sequence, known as the microsatellite instability (MSI) phenotype, accounts for roughly 10% of the patients and derives from polyps with a serrated morphology.
BRAF-mutated polyps were more likely than KRAS-mutated polyps to arise in a precursor polyp (82% versus 18%, P < 0.001), and were more likely to have slit-like serrations (100% versus 73%, P = 0.003).
These results illustrate the importance of RNF43, along with BRAF mutation in the serrated neoplasia pathway (both the sporadic and familial forms), inform genetic diagnosis protocol and raise therapeutic opportunities through Wnt inhibition in different stages of evolution of serrated polyps.
Patients were classified into 3 subgroups, based on the polyp mutational profile at baseline, as follows: non-mutated polyps (Wild-type), at least one BRAF-mutated polyp, or at least one KRAS-mutated polyp.
The contention is that BRAF inhibitor induced polyps mimic the afore-described histology and molecular features of serrated polyps with the exception that instead of the presence of <i>BRAF</i> mutations they induce C-RAF homodimers and B-RAF: C-RAF heterodimers.
The aim of this study was to investigate BRAF mutation and DNA methylation in colorectal serrated polyps and the right colon.Between 2005 and 2013, 146 colon polyps (47 tubular adenomas [TAs], 53 traditional serrated adenomas [TSAs], 17 sessile serrated adenomas/polyps [SSAs], and 29 hyperplastic polyps in the proximal colon [PHPs]) were collected from patients.
Histologically, BRAF mutation was associated with a poorly differentiated histology, a serrated precursor polyp and focal signet ring cell differentiation (p=0.042, 0.008 and 0.008, respectively).
BRAF-mutated index TSAs were strongly associated with a right-sided location and BRAF mutation of synchronous/metachronous serrated polyps (P = 0.013 and P = 0.005, respectively).
BRAF mutant traditional serrated adenomas were more frequently proximal (39% versus 2%; P≤0.0001), were exclusively associated with a precursor polyp (57% versus 0%; P≤0.0001), and were more frequently CpG island methylator phenotype high (60% versus 16%; P≤0.0001) than KRAS mutant traditional serrated adenomas.
We proposed that immunohistochemical detection of BRAF((V600E)) using a BRAF((V600E)) mutation-specific antibody is a feasible technique for reproducibly identifying proximal serrated polyps with malignant potential in clinical practice, which may need more aggressive treatment and vigilant clinical monitoring.
A per-patient analysis revealed that all patients had a BRAF or KRAS mutation in more than 25% of their polyps; 84.8% of patients had a mutation in BRAF or KRAS in more than 50% of their polyps.
Risk factors for CIMP-high-serrated lesions included Caucasian race, current smoking status, and a history of polyps, whereas for serrated lesions with mutant BRAF, the significant risk factors were male sex, current smoking status, obesity, and a history of polyps.
Previous studies demonstrated a high prevalence of a BRAFp.V600E mutation in perineuriomas with serrated crypts and suggested that perineuriomas without crypt serration may represent an unrelated, different type of polyp.