Expression of Glucose Metabolism-Related Proteins in Adrenal Neoplasms

Abstract

Purpose: The aim of this study was to investigate the expression patterns of glucose metabolism-related proteins and their clinicopathologic implications in adrenal cortical neoplasms (ACN) and pheochromocytoma (PCC).

Methods: Immunohistochemical staining was performed to evaluate glucose metabolism-related proteins (GLUT1, CAIX, hexokinase II, G6PDH, PHGDH, and SHMT1) in 132 ACN cases (115 adrenal cortical adenoma [ACA] and 17 adrenal cortical carcinoma [ACC]) and 189 PCC cases.

Results: Expression levels of GLUT1 in tumor cells ([T]; p < 0.001), GLUT1 in stromal cells ([S]; p < 0.001), G6PDH (p < 0.001), and SHMT1 (p = 0.002) were higher in ACN than in PCC. GLUT1 (T; p = 0.045) and PHGDH (p = 0.043) levels were higher in ACC than in ACA. In a univariate analysis of ACN, GLUT1 (T; p = 0.017), CAIX (S; p = 0.003), and PHGDH (p = 0.009) levels were correlated with a shorter overall survival (OS). GLUT1 (T; p = 0.001) and PHGDH (p < 0.001) were related to a shorter OS in PCC. GLUT1 (T) positivity (p = 0.043) in ACN predicted a poor OS in a multivariate Cox analysis. In PCC, high GAPP score (p = 0.026), GLUT1 (T; p = 0.002), and PHGDH (p < 0.001) were independent prognostic factors for poor OS.

Conclusions: The adrenal gland tumors ACN and PCC had different expression patterns of glucose metabolism-related proteins (GLUT1, G6PDH, and SHMT1), with higher expression levels in ACN than in PCC. GLUT1 and PHGDH were significant prognostic factors in these adrenal neoplasms.