Immunohistochemical Analysis of the Metabolic Phenotype of Adrenal Cortical Carcinoma

AbstractMetabolic reprogramming is a cellular process contributing to carcinogenesis. However, it remains poorly understood in adrenal cortical carcinoma (ACC), an aggressive malignancy with overall poor prognosis and limited therapeutic options. We characterized the metabolic phenotype of ACC, by examining the immunoprofile of key proteins involved in glucose metabolism, hexokinase (HK1), pyruvate kinase (PKM1, PKM2), succinate dehydrogenase (SDHB), and phospho-S6 ribosomal protein (pS6), in a tissue microarray of 137 adrenal cortical tissue samples. Protein expression was compared between ACC (n = 42), adrenal cortical adenoma (ACA;n = 50), and normal adrenal cortical tissue samples (n = 45). Cytoplasmic expression of HK1 and PKM2 was significantly higher in ACC than in ACA (p <  0.001 andp = 0.014, respectively) or normal adrenal cortical tissue samples (p <  0.001 andp <  0.001, respectively). Expression of HK1 and PKM2 was also higher in ACA than in normal adrenal cortical tissue samples (p <  0.001 andp <  0.001, respectively). PKM1 expression was overall low in ACC, ACA, and normal samples, although expression of PKM1 was higher in ACC than in ACA (p = 0.027). There was no loss of cytoplasmic granular SDHB expression in our cohort of adrenal cortical tumors, and cytoplasmic expression of pS6 was lower in ACC than in ACA (p = 0.003) or normal adrenal cortical tissue samples (p = 0.008). Significantly, HK1 expression cor...
Source: Endocrine Pathology - Category: Pathology Source Type: research