Traditional serrated adenoma with BRAF mutation is associated with synchronous/metachronous BRAF-mutated serrated lesions.
OBJECTIVE
To determine whether traditional serrated adenoma (TSA) results in an increased risk of developing subsequent serrated polyps or colorectal cancer (CRC).


RESULTS
We recruited 111 patients with an index TSA, and analysed the pathological and molecular features of their synchronous/metachronous serrated lesions. Fifty hyperplastic polyps, 14 sessile serrated adenomas, an additional 27 TSAs and 17 CRCs were identified from 46 patients. Twenty-seven percent of TSAs showed a precursor serrated polyp in the periphery and were strongly correlated with BRAF mutation (P < 0.001). Serrated polyps occurred more commonly in patients with BRAF-mutated index TSAs than in patients with KRAS-mutated index TSAs. 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). The 17 CRCs occurred more frequently in women, and were characterized by a high BRAF mutation rate (59%), a positive CpG island methylator phenotype (59%), and stable or low levels of microsatellite instability (77%).


CONCLUSIONS
BRAF-mutated TSA is distinct from KRAS-mutated TSA in predisposing to the acquisition of subsequent serrated neoplasia. This indicates the presence of an intestinal field defect in the tumour microenvironment that results in tumour initiation and malignant progression.
Department of Pathology, National Taiwan University, Taipei, Taiwan.|Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Jia-Huei
JH
Tsai
Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
Chien-Hsuan
CH
Cheng
Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
Chien-Chuan
CC
Chen
Department of Oncology, National Taiwan University, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yu-Lin
YL
Lin
Department of Laboratory Medicine, National Taiwan University, Taipei, Taiwan.|Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Liang-In
LI
Lin
Department of Pathology, National Taiwan University, Taipei, Taiwan.
Mei-Ling
ML
Chen
Department of Pathology, National Taiwan University, Taipei, Taiwan.|Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Jau-Yu
JY
Liau
D000236:Adenoma / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D000368:Aged; D003111:Colonic Polyps / Q000235:genetics / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
C117307:KRAS protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)
BRAF; KRAS; colorectal cancer; serrated neoplasia; serrated pathway; synchronous and metachronous; traditional serrated adenoma