Expression of glutamine metabolism-related proteins in Hürthle cell neoplasm of thyroid: Comparison with follicular neoplasm

Abstract

Purpose. We evaluated the expression of glutaminolysis-related proteins in Hurthle cell neoplasms (HCN) and follicular neoplasms (FN) of the thyroid, and investigated its clinical implication. Methods. Tissue microarrays were constructed from 264 FNs (112 follicular carcinomas [FCs] and 152 follicular adenomas [FAs]) and 108 HCNs (27 Hurthle cell carcinomas [HCCs] and 81 Hurthle cell adenomas [HCAs]. The immunohistochemical staining result of 3 glutaminolysis-related proteins (Glutaminase 1 [GLS1], glutaminate dehydrogenase [GDH] and alanine- serine, cysteine-preferring transporter 2 [ASCT2]) was analyzed. Results. GLS1 and GDH showed significantly higher expression rates in HCN compared to FN (P<0.001). More HCN cases showed co-positivity of multiple glutaminolysis-related proteins than those of FN cases (P<0.001). In silico analysis, both GLUD1 and GLUD2 showed higher expression rate in HCA compared to FA (P=0.027 and P=0.018, respectively). SLC1A5 expression was highest in HCA, followed by FC and FA (HCA vs FC, P=0.023; FC vs FA, P=0.002). Conclusion. FN and HCN exhibit a different expression pattern for glutaminolysis-related proteins, and GLS1 and GDH have higher expression rates in HCN and FN.