The Risk of Relapse in Papillary Thyroid Cancer (PTC) in the Context of BRAFV600E Mutation Status and Other Prognostic Factors

PLoS One. 2015 Jul 15;10(7):e0132821. doi: 10.1371/journal.pone.0132821. eCollection 2015.

Abstract

Introduction: The risk of over-treatment in low-advanced PTC stages has prompted clinicians to search for new reliable prognostic factors. The presence of BRAF mutation, the most frequent molecular event in PTC, seems to be a good candidate. However, there is still lack of randomised trials and its significance has been proved by retrospective analyses, involving a large group of patients. The question arises whether this factor is useful in smaller populations, characterised for specialised centres. Thus, the aim of the study was to evaluate the use of BRAF mutation as a potential predictive marker in PTC patients.

Material: 233 PTC subjects treated between 2004-2006, were retrospectively analysed. Stage pT1 was diagnosed in 64.8% patients and lymph node metastases in 30.9%. Median follow-up was 7.5 years. BRAFV600E mutation was assessed postoperatively in all cases.

Results: BRAF V600E mutation was found in 54.5%. It was more frequent in patients > 45 years (p=0.0001), and associated with larger tumour size (p=0.004). Patients with tumours <= 10 mm were over-represented among BRAF negative population (p=0.03). No association between BRAF mutation and other clinicopathological factors was observed. BRAF status was associated neither with relapse nor with disease-free survival (DFS) (p=0.76). Nodal status, extrathyroidal invasion and tumour size significantly influenced DFS.

Conclusion: The risk of PTC recurrence is mainly related to the presence of lymph node metastases and extrathyroidal invasion, whereas no impact of BRAF V600E mutation has been demonstrated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Substitution
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / genetics
  • Carcinoma / diagnosis*
  • Carcinoma / genetics*
  • Carcinoma / mortality
  • Carcinoma / pathology
  • Carcinoma, Papillary
  • Female
  • Gene Frequency
  • Glutamic Acid / genetics
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Predictive Value of Tests
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics*
  • Recurrence
  • Risk Factors
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / diagnosis*
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / mortality
  • Thyroid Neoplasms / pathology
  • Valine / genetics

Substances

  • Biomarkers, Tumor
  • Glutamic Acid
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Valine

Grants and funding

The study was partially funded by Polish National Science Center grant NN 403 194340 to A.C. The study was also conducted as an internal research project in MSC Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.