Abstract
The aim of the study was to investigate the expression of serine/glycine-related proteins in Hürthle cell neoplasm (HCN) and follicular neoplasm (FN) and to explore its associated implications. Tissue microarrays were constructed with 265 cases of FN (follicular carcinoma [FC]: 112 and follicular adenoma [FA]: 153) and 107 cases of HCN (Hürthle cell carcinoma [HCC]: 27 and Hürthle cell adenoma [HCA]: 80). The serine/glycine-related proteins PHGDH, PSAT1, SHMT1, and GLDC were evaluated using immunohistochemical staining. The expression of SHMT1 and PHGDH was higher in HCN compared to FN (P<0.001 and P=0.048). SHMT1 expression was highest in HCC, followed by HCA, FA, and FC (P<0.001), and PHGDH expression was highest in HCA, followed by HCC, FC, and FA (P=0.041). In FC, SHMT1 negativity was associated with extrathyroidal extension (P=0.019). In univariate analysis, PSAT1 negativity was associated with shorter overall survival (P<0.001). The expression of serine/glycine-related proteins differed between FN and HCN. The expression of both SHMT1 and PHGDH was higher in HCN compared to FN. The clinical implications of this study are that the serine/glycine metabolism pathway could be a possible therapeutic target in HCC.