The prognostic significance of the BRAF V600E mutation in papillary thyroid carcinoma detected by mutation-specific immunohistochemistry

Pathology. 2013 Dec;45(7):637-44. doi: 10.1097/PAT.0000000000000008.

Abstract

Aims: BRAF mutation has been shown in a large meta-analysis to be an independent prognostic marker for papillary thyroid carcinoma (PTC) with poorer survival and higher recurrence rates.

Methods: We studied prevalence of BRAF mutation in 77 patients with PTC from an Australian cohort using competitive polymerase chain reaction (C-PCR) and immunohistochemistry (IHC) with BRAF-specific antibody, VE1. Clinicopathological parameters, recurrence and mortality were analysed according to BRAF mutation status.

Results: Median follow-up was 84.5 months. BRAF mutation was demonstrated in 65% of cases combining both C-PCR and IHC; in 71% (37/77) of tumours >1 cm and 52% (13/25) of microcarcinomas (<1 cm). IHC was positive in 69% (49/71) and C-PCR in 53% (41/77); 87% (67/77) of our patients were treated with total thyroidectomy and 65% (50/77) also had radioactive ablation. BRAF positive tumours had a significantly higher rate of subsequent lymph node metastases (p=0.035). Significant association was found between BRAF mutation and male sex (p=0.034), but not between age >45 years at diagnosis, size of primary tumour, extrathyroidal extension, lymph node or distant metastases or clinical stage at diagnosis.

Conclusions: BRAF mutation in PTC determined by IHC is associated with significantly increased risk of lymph node recurrence.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / metabolism
  • Carcinoma, Papillary / mortality
  • Carcinoma, Papillary / pathology
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins B-raf / metabolism
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / mortality
  • Thyroid Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins B-raf