Predictive molecular pathology in metastatic thyroid cancer: the role of RET fusions

ABSTRACT

Background

Rearranged during transfection (RET) gene fusions are detected in 10–20% of thyroid cancer patients. Recently, RET fusion-positive metastatic thyroid cancers have attracted much attention owing to the FDA approval of two highly selective anti-RET tyrosine kinase inhibitors, namely, selpercatinib, and pralsetinib.

Areas covered

This review summarizes the available evidence on the biological and predictive role of RET gene fusions in thyroid carcinoma patients and the latest screening assays currently used to detect these genomic alterations in histological and cytological specimens.

Expert opinion

Management of advanced thyroid carcinoma has significantly evolved over the last decade thanks to the approval of three multikinase inhibitors, i.e. sorafenib, lenvatinib, cabozantinib, and of two selective RET-tyrosine inhibitors, i.e. selpercatinib and pralsetinib. In this setting, the detection of RET-fusions in advanced thyroid cancer specimens through the use of next-generation sequencing has become a commonly used strategy in clinical practice to select the best treatment options.

KEYWORDS:

• Thyroid cancer
• RET fusion
• molecular pathology
• selpercatinib
• pralsetinib

Article highlights

• Thyroid carcinoma represents the nnthcause of new cancer diagnosis worldwide, as estimated in 2020

• RET gene fusions are detected in about 10–20% of PTCs, and less frequently (<10%) in other thyroid cancer types, including follicular, Hürthle-cell, poorly differentiated, and anaplastic carcinomas

• More recently, there has been growing interest in RET fusion-thyroid cancers owing to the FDA-approval of RET-specific tyrosine kinase inhibitors (TKIs), namely selpercatinib and pralsetinib

• Next-generation sequencing is a robust and sustainable tool for advanced thyroid cancer patients

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Conceptualization: Mariantonia Nacchio, Pasquale Pisapia, Francesco Pepe, Giancarlo Troncone, Umberto Malapelle, Claudio Bellevicine; Methodology, all authors; Software: all authors; Validation, all authors; Formal Analysis: all authors; Investigation: all authors; Resources: all authors; Data Curation: all authors; Writing – Original Draft Preparation: Mariantonia Nacchio, Pasquale Pisapia, Francesco Pepe; Writing – Review and Editing: all authors; Visualization: all authors; Supervision: Giancarlo Troncone, Umberto Malapelle, Claudio Bellevicine; Project Administration, Giancarlo Troncone, Umberto Malapelle, Claudio Bellevicine.

Additional information

Funding

This paper was not funded.