Frequent BRAF mutation in early-onset colorectal cancer in Taiwan: association with distinct clinicopathological and molecular features and poor clinical outcome.
BACKGROUND
Occurrence of early-onset colorectal cancer (EOCRC) under the age of 30 is very rare and the molecular characteristics are poorly understood. A low BRAF mutation rate has been noted in several studies of EOCRC from Western countries.


OBJECTIVE
To determine the clinicopathological and molecular features of EOCRCs in Taiwan.


METHODS
KRAS/BRAF gene mutation, mismatch repair protein immunohistochemistry, microsatellite instability and CpG island methylation phenotype analyses were examined to determine the molecular characteristics of EOCRC.


RESULTS
Sixty-six patients with EOCRC at our hospital between 2000 and 2012 were studied. BRAF mutation was detected in 11 of the 59 tumours analysed (19%) and the rate was significantly higher than the overall BRAF mutation rate of colorectal cancer in patients older than 30 years (p<0.001). Clinically, 9 of 11 patients with BRAF-mutated tumours presented with advanced-stage diseases and they presented significantly more frequently with stage IV disease than those with BRAF wild-type tumours (p=0.042). 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). None of the BRAF-mutated tumours was mismatch repair protein-deficient and/or microsatellite instability-high. Overall survival of patients with BRAF-mutated tumours was significantly worse than that of patients with BRAF wild-type tumours, despite adjustment for the disease stages and tumour differentiation.


CONCLUSIONS
BRAF mutation was frequent in EOCRCs in Taiwan and was associated with distinct clinicopathological and molecular features.
Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Jia-Huei
JH
Tsai
Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Jau-Yu
JY
Liau
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yu-Lin
YL
Lin
Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
Li-Hui
LH
Tseng
Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Liang-In
LI
Lin
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Kun-Huei
KH
Yeh
Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yung-Ming
YM
Jeng
D000328:Adult; D017668:Age of Onset; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013624:Taiwan
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
COLORECTAL CANCER; MOLECULAR PATHOLOGY; ONCOLOGY