Prevalence and Impact of BRAF mutation in patients with concomitant papillary thyroid carcinoma and Hashimoto's thyroiditis: a systematic review with meta-analysis

Front Endocrinol (Lausanne). 2023 Nov 17:14:1273498. doi: 10.3389/fendo.2023.1273498. eCollection 2023.

Abstract

Background: Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC in patients with both diseases concomitantly has been found to be more indolent than conventional PTC. Additionally, it has been well proven that BRAF mutation results in an aggressive course of PTC. The aims of this meta-analysis were to identify prevalence of BRAF mutation and its impact on clinicopathological features in patients with concomitant PTC-HT.

Methods: Medline, Cochrane Library, Scopus, and Web of Science were searched until 16.09.2022, resulting in 227 articles, of which nine studies were included. Summary estimates, comparing patients with (A) BRAF (+) PTC-HT versus BRAF (+) PTC, and (B) BRAF (+) PTC-HT versus BRAF (-) PTC-HT, were generated with Review Manager 5.0.

Results: In total, 6395 patients were included in this review. PTC-HT patients had significantly less BRAF mutation than PTC patients (Odds Ratio (OR) (95% Confidence Interval (CI))=0.45 (0.35-0.58), P<0.001). BRAF (+) PTC-HT patients were significantly more likely to have multifocal lesions (OR (95% CI)=1.22 (1.04-1.44), P=0.01) but less likely to have lymph node metastasis (OR (95% CI)=0.65 (0.46-0.91), P=0.01) and extrathyroidal extension (OR (95% CI)=0.55 (0.32-0.96), P=0.03) compared to BRAF (+) PTC patients. BRAF (+) PTC-HT patients were more likely to have multifocal lesions (OR (95% CI)=0.71 (0.53-0.95), P=0.02), lymph node metastasis (OR (95% CI)=0.59 (0.44-0.78), P<0.001) and extrathyroidal extension (OR (95% CI)=0.72 (0.56-0.92), P=0.01) compared to BRAF (-) PTC-HT patients.

Conclusion: This meta-analysis highlights that the lower prevalence of BRAF mutation in patients with PTC-HT than conventional PTC may explain the indolent clinicopathological course in this cohort.

Keywords: BRAF mutation; Hashimoto thyroiditis; extrathyroidal extension; lymph node metastasis; multifocality; papillary thyroid carcinoma.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Carcinoma, Papillary* / complications
  • Carcinoma, Papillary* / epidemiology
  • Carcinoma, Papillary* / genetics
  • Hashimoto Disease* / complications
  • Hashimoto Disease* / epidemiology
  • Hashimoto Disease* / genetics
  • Humans
  • Lymphatic Metastasis
  • Mutation
  • Prevalence
  • Proto-Oncogene Proteins B-raf / genetics
  • Thyroid Cancer, Papillary / complications
  • Thyroid Cancer, Papillary / epidemiology
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Neoplasms* / epidemiology
  • Thyroid Neoplasms* / genetics
  • Thyroid Neoplasms* / pathology

Substances

  • Proto-Oncogene Proteins B-raf
  • BRAF protein, human

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.