Genetic Changes in Thyroid Cancers and the Importance of Their Preoperative Detection in Relation to the General Treatment and Determination of the Extent of Surgical Intervention—A Review

Abstract

Carcinomas of the thyroid gland are some of the most common malignancies of the endocrine system. The causes of tumor transformation are genetic changes in genes encoding cell signaling pathways that lead to an imbalance between cell proliferation and apoptosis. Some mutations have been associated with increased tumor aggressiveness, metastatic lymph node spread, tendency to dedifferentiate, and/or reduced efficiency of radioiodine therapy. The main known genetic causes of thyroid cancer include point mutations in the BRAF, RAS, TERT, RET, and TP53 genes and the fusion genes RET/PTC, PAX8/PPAR-γ, andNTRK. Molecular genetic testing of the fine needle aspiration cytology of the thyroid tissue in the preoperative period or of the removed thyroid tissue in the postoperative period is becoming more and more common in selected institutions. Positive detection of genetic changes, thus, becomes a diagnostic and prognostic factor and a factor that determines the extent of the surgical and nonsurgical treatment. The findings of genetic research on thyroid cancer are now beginning to be applied to clinical practice. In preoperative molecular diagnostics, the aggressiveness of cancers with the most frequently occurring mutations is correlated with the extent of the planned surgical treatment (radicality of surgery, neck dissection, etc.). However, clear algorithms are not established for the majority of genetic alterations. This review aims to provide a basic overview of the findings of the most commonly occurring gene mutations in thyroid cancer and to discuss the current recommendations on the extent of surgical and biological treatment concerning preoperatively detected genetic changes.

Age and BRAFV600E Mutation Stratified Patients with Cytologically Benign Thyroid Nodules

“… 8 The main known genetic causes of thyroid cancer include point mutations in the BRAF, RAS, TERT, RET , and TP53 genes and the fusion genes RET/PTC, PAX8/PPAR-γ , and NTRK . 9 Fusion gene positive PTCs were associated with more aggressive behavior disease than fusion gene negative PTCs. 10 A comprehensive study reported by Pekova et al recently identified that RET fusion was associated with a 100% probability of malignancy.…”

Recent Trends and Potential of Radiotherapy in the Treatment of Anaplastic Thyroid Cancer

“…This mutation activates BRAF kinase, which phosphorylates multiple targets, including MEK and ERK [ 49 ]. The BRAF V600E mutation is observed in approximately 20–40% of ATCs [ 50 ], and Jannin et al [ 12 ]. reported that the frequency of BRAF mutations in ATCs appears to vary in each region.…”

The current assessment and management of thyroid nodules

“…Although, FNA differentiates benign from malignant thyroid nodules in an appropriate manner, in approximately 30% of patients persists diagnostic difficulties for nodules categorized with indeterminate cytology, comprising atypia of undetermined significance or follicular lesion of undetermined significance (TBSRTC III, AUS/FLUS) and follicular neoplasm (TBSRTC IV, FN/SFN) or Hürthle cell neoplasm (TBSRTC IV, HCN/SHCN) [42,43]. The AAES recommends for TBSRTC III nodules, in addition to the other guidelines, to reckon with clinical factors, radiologic features, and patient preference about repeat biopsy, molecular testing, diagnostic thyroidectomy, or observation [2,4,6].…”