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Frequent BRAF mutation in early-onset colorectal cancer in Taiwan: association with distinct clinicopathological and molecular features and poor clinical outcome
  1. Jia-Huei Tsai1,2,
  2. Jau-Yu Liau1,2,
  3. Yu-Lin Lin3,4,
  4. Li-Hui Tseng5,
  5. Liang-In Lin6,7,
  6. Kun-Huei Yeh3,4,8,
  7. Yung-Ming Jeng1,2
  1. 1Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
  2. 2Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan
  3. 3Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
  4. 4Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
  5. 5Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
  6. 6Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
  7. 7Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan
  8. 8Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan
  1. Correspondence to Dr Yung-Ming Jeng, Department Pathology, National Taiwan University Hospital, No 7, Chung-Shan South Road, Taipei 10051, Taiwan; mrna0912{at}yahoo.com.tw

Abstract

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.

Aims 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.

  • COLORECTAL CANCER
  • MOLECULAR PATHOLOGY
  • ONCOLOGY

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