Abstract / Summary
Background: /Objectives: Anaplastic thyroid cancer (ATC) is a rare and highly aggressive thyroid malignancy with limited treatment options. Loss of the sodium/iodide symporter makes ATC resistant to radioactive iodine therapy, highlighting the need for alternative therapeutic targets. This study evaluated L-type amino acid transporter 1 (LAT-1) and vitamin D receptor (VDR) as potential targets in ATC.
Methods: We examined LAT-1 (SLC7A5) and VDR gene expression using TCGA data from the UALCAN database. Protein expression was evaluated by immunohistochemistry in 28 formalin-fixed, paraffin-embedded ATC specimens from Loma Linda University Health. We assessed staining intensity and distribution and compared expression between male and female patients.
Results: TCGA analysis showed significantly higher SLC7A5 expression in thyroid tumors compared with normal thyroid tissue (*p = 0.0115), while VDR was strongly increased in tumors (**p < 0.001) and across all tumor stages. All 28 ATC specimens expressed both LAT-1 and VDR, although staining intensity and distribution varied among tumors. LAT-1 was primarily localized to the membrane and cytoplasm of tumor cells, with additional expression in stromal and endothelial cells. VDR showed membranous, cytoplasmic, and occasional nuclear expression. LAT-1 expression did not differ significantly by sex (ns, not significant, p = 0.19), whereas VDR expression was significantly higher in females than males (**p = 0.0014).
Conclusions: LAT-1 and VDR are broadly expressed in ATC despite substantial intratumoral heterogeneity. Their consistent expression supports further investigation as potential targets for radioligand or other ligand-directed therapies. The higher VDR expression observed in female patients also suggests a potentially important sex-associated difference that warrants validation in larger ATC cohorts.