SEAP-GETNE consensus on prognostic and predictive molecular biomarkers in thyroid cancer.

Thyroid cancer is the most common endocrine malignancy and generally carries a favourable prognosis. However, a subset of cases exhibits aggressive behaviour, metastatic potential, and resistance to conventional therapies. The 2022 WHO classification introduced major updates, including refined subtypes of papillary thyroid carcinoma (PTC), recognition of high-grade follicular cell-derived carcinomas, and the introduction of grading criteria for medullary thyroid carcinoma (MTC). These revisions reflect advances in tumour biology and are essential for precise diagnosis and treatment planning. Molecular profiling has become central to the management of thyroid cancer. Key driver mutations in follicular cell-derived tumours include BRAF V600E (common in PTC), RAS mutations (common in follicular carcinomas), and RET, NTRK, and ALK gene fusions, all of which influence prognosis and therapeutic strategies. MTC is primarily driven by RET and RAS mutations. In anaplastic thyroid carcinoma (ATC), the most aggressive subtype, evaluation of PD-L1 expression and BRAF mutations is recommended to guide treatment. Accurate molecular analysis depends on appropriate tumour sample selection and processing. Genetic testing is particularly indicated in advanced, refractory, or metastatic disease to identify candidates for targeted therapies, which have shown significant clinical benefit. Two diagnostic strategies are proposed: a sequential single-gene approach, typically beginning with BRAF testing, or comprehensive profiling using next-generation sequencing (NGS). Multidisciplinary molecular tumour boards are strongly recommended to integrate histological, molecular, and clinical information for personalised treatment decisions.