IGF2BP1 is the first positive marker for anaplastic thyroid carcinoma diagnosis

• DOI: 10.1038/s41379-020-0630-0
• Publication Date: 2020-07-27T18:03:48Z
• Authors: Jacob Haase; Danny Misiak; Marcus Bauer; Nikolaos Pazaitis; Juliane Braun; Rebecca Pötschke; Alexander Mensch; Jessica Lilian Bell; Henning Dralle; Udo Siebolts; Claudia Wickenhauser; Kerstin Lorenz; Stefan Hüttelmaier
• Keywords: Tissue microarray

Anaplastic thyroid carcinomas (ATC) are rare, but represent the most lethal malignancy of thyroid. Selective molecular markers and drivers distinguishing ATC from other follicular origin remain largely unknown, limiting advances in diagnosis treatment. In a retrospective study, we analyzed gene expression 36 ATC, 18 poorly differentiated, 132 papillary, 55 carcinoma, as well 124 paired unpaired normal tissues three independent cohorts by RNA-sequencing immunohistochemistry. data test cohort suggested selective protein biomarkers. Evaluation these revealed that ATCs characterized de novo various testis antigens, including melanoma-associated antigen A3 (MAGEA3), importantly oncofetal IGF2 mRNA binding 1 (IGF2BP1). Shallow whole genome sequencing essentially excluded IGF2BP1 upregulation results copy number alterations. Immunohistochemical analyses all tumor confirmed ATC. sum, 75% (27/36) tested 0.5% (1/204) well-differentiated carcinoma tissue samples were positive for protein. This indicates identifies with diagnostic odds ratio 612 (95% CI: 74.6–5021). addition, found MAGEA3 is exclusively, although less consistently upregulated presenting an 411 23.8–7098.7). Importantly, provide confirmatory evidence distinguishes differentiated carcinoma. furthermore identified foci within low-grade conclusion, represents promising single-gene marker available followed MAGEA3, improving on current techniques. Robust essential to help distinguish this high-grade carcinomas, guide surgical decision making, therapy post-resection/therapy monitoring strategies.