Endocrine Abstracts

Background: Thyroid cancer is the most frequent endocrine malignancy, with >7000 cases diagnosed in central Europe every year. Recently, ALK/EML4 translocations have been reported in single cases in anaplastic thyroid cancer (ATC). Little is known about the frequency of ALK alterations in poorly differentiated thyroid cancer (PTC). Our aim was to investigate the frequency of ALK alterations in patients with advanced thyroid carcinomas.

Material and methods: Formalin-fixed and paraffin embedded (FFPE) samples of 60 ATC and 55 PTC were analyzed. Five samples of goiters served as controls. FFPE samples were investigated immunohistochemically with different antibodies against ALK (clone D5F3, Cell Signaling Technology, and clone 5A4, Leica Biosystems). Stainings were analyzed quantitatively using a grid ocular, with an arbitrarily cut-off level of 10%. Additionally, fluorescence in situ (FISH) analysis was performed on tissue microarrays using Vysis ALK Break apart FISH probe (Abbott Laboratories), with a cut-off level of 15%.

Results: Of all investigated thyroid cancers, 10% of ATC and 27% of PTC showed immunohistochemically a light to moderate nuclear staining for ALK. All five controls were negative for ALK. FISH analysis showed single breaks without reaching the cut-off level for ALK/EML4 translocations.

Discussion: The occurrence of ALK/EML4 translocations is a rare event in ATC and PTC, with no verifiable case in our series. However, in contrast to the reported ALK-stainings, which were cytoplasmatic, we found a nuclear positivity in 10% of ATC and 27% of PTC, which has been not described in thyroid cancers so far. According to the recently described RANBP2-ALK translocation in epitheloid inflammatory myofibroblastic sarcoma, which show a nuclear ALK expression in immunohistochemical staining, further studies are necessary to clarify the significance of nuclear ALK stainings in thyroid carcinoma, and a possible different break event of the ALK gene.