Clinico-pathological factors associated with BRAF-V600E mutation in colorectal serrated adenomas

Serrated adenomas are genetically heterogeneous, and the histological classification into sessile serrated (SSA) adenoma and traditional serrated adenoma (TSA) does not reflect the molecular landscape. The objective of this study was to assess clinical or pathological factors associated with BRAF-V600E mutation in serrated adenomas. Systematic review and meta-analysis was performed by searching electronic databases from January 2011 to January 2019 for studies assessing the association of BRAF-V600E mutation with clinical or pathological features of serrated adenomas. Odds ratio (OR) was calculated for each factor; a P-value <0.05 was considered significant. Forty studies assessing 3511 serrated adenomas (2375 SSAs and 1136 TSAs) were included. 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. Conversely, BRAF mutation was not associated with age <70 years (OR = 1.63; P = 0.34), age <60 years (OR = 0.86; P = 0.79), female sex (OR = 0.77; P = 0.12), flat morphology (OR = 1.52; P = 0.16), presence of any dysplasia (OR = 1.01; P = 0.59), serrated dysplasia (OR = 1.23; P = 0.72) and invasive cancer (OR = 0.67; P = 0.32), nuclear b-catenin expression (OR = 0.73; P = 0.21) and p53 overexpression (OR = 1.24; P = 0.82). In conclusion, BRAFV600E mutation is associated with proximal localisation and CIMP-H status in both SSA and TSA, with size <10 mm only in TSA, and with expression of MUC5A5 and MUC6 and endoscopic pit pattern II-O at least in SSA. In serrated adenomas, BRAF-V600E mutation does not seem to be associated with age and sex, with the prevalence of dysplasia and cancer and with the morphology of the dysplastic component.