Gamma-glutamyl cyclotransferase, a molecule identified from the invasive front of follicular thyroid carcinoma, is useful for differential diagnosis of follicular thyroid tumors

Pathol Res Pract. 2024 Oct 28:264:155678. doi: 10.1016/j.prp.2024.155678. Online ahead of print.

Abstract

We aimed to establish a useful molecular marker for differentiating between follicular thyroid carcinoma (FTC) and follicular adenoma (FA). RNA was extracted from the invasive front and paired tumor center tissues from three FTC cases using laser microdissection for cDNA microarray analysis, revealing high expression of gamma-glutamyl cyclotransferase (GGCT) in the invasive front. Subsequently, immunohistochemical (IHC) staining of GGCT was performed with formalin-fixed paraffin-embedded (FFPE) sections of FTC (n = 32), FA (n = 64), and follicular tumor of uncertain malignant potential (FT-UMP, n = 5). The GGCT expression score (range: 0-300) was calculated by multiplying the intensity score (0-3) and percentage of positive cells. The Ki-67 labeling index was also assessed in 20 FTC and 25 FA cases from the same cohort. The GGCT expression score was higher in FTC than in FA (118.5 ± 51.4 vs. 57.3 ± 34.7, P < 0.0001). With the GGCT expression score, using a cutoff value of 101.1, the differentiation between FTC and FA was possible with a sensitivity of 68.8 % and specificity of 87.5 % (AUC = 0.832). With the Ki-67 labeling index, applying a cutoff value of 4.0 %, the distinction between FTC and FA resulted in a sensitivity of 50.0 % and specificity of 80.0 % (AUC = 0.677). The GGCT expression score was positively related to the Ki-67 labeling index in the FTC cases. (Spearman's ρ = 0.5293, P = 0.0164). Therefore, GGCT is a potential marker for differentiating FTC from FA. The GGCT expression of FTC may be indicative of its invasive and proliferative activity.

Keywords: Follicular adenoma; Follicular thyroid carcinoma; Gamma-glutamyl cyclotransferase; Invasion; Invasive front; Ki-67; Thyroid gland.