Clinicopathological significance of major fusion oncogenes in papillary thyroid carcinoma: An individual patient data meta-analysis

Pathol Res Pract. 2022 Dec:240:154180. doi: 10.1016/j.prp.2022.154180. Epub 2022 Oct 21.

Abstract

Introduction: Fusion oncogenes (e.g., NTRK, RET, ALK, BRAF) are rare genetic events in papillary thyroid carcinoma (PTC). It is still unclear regarding the similarities and differences in clinicopathological manifestations and prognostic outcomes of these genetic alterations. This individual patient data (IPD) meta-analysis analyzed the clinicopathological significance and prognoses of different types of oncogenic fusions in PTC patients.

Methods: Categorical variables were compared by using Chi-square and Fisher's exact tests while Wilcoxon rank-sum and analysis of variance (ANOVA) tests were utilized for continuous covariates. Progression-free survival (PFS) and overall survival (OS) were computed using Kaplan-Meier analysis and log-rank test.

Results: We included 27 studies for meta-analyses. NTRK-, RET-, BRAF-, and ALK-rearranged PTCs had a unique demographic/clinicopathological profile but similar PFS and OS. NTRK1-positive PTCs demonstrated more aggressive clinical behaviors and shorter PFS in comparison to NTRK3-positive PTCs whereas RET rearrangement variants shared comparable clinicopathological backgrounds.

Conclusion: This study provides new insights and facilitates our current understanding of clinicopathological features and survival outcomes of different fusion oncogenes in PTCs. It may help clinicians better counsel the patients and tailor appropriate treatment decisions.

Keywords: ALK; BRAF; NTRK; PPARG; Papillary thyroid carcinoma; RET.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Carcinoma, Papillary* / genetics
  • Carcinoma, Papillary* / pathology
  • Gene Rearrangement
  • Humans
  • Mutation
  • Oncogenes / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Receptor Protein-Tyrosine Kinases / genetics
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Neoplasms* / pathology

Substances

  • Proto-Oncogene Proteins B-raf
  • Receptor Protein-Tyrosine Kinases