Autophagy-Related Proteins Are Differentially Expressed in Adrenal Cortical Tumor/Pheochromocytoma and Associated with Patient Prognosis.

Hye Min Kim,Ja Seung Koo

doi:10.3390/ijms221910490

Abstract

The aim of this research was to evaluate the expression and concomitant implications of LC3A, LC3B, beclin-1, and p62, which are key components of autophagy in human adrenal gland tumors. Tissue microarray was made for 321 cases of adrenal gland tumor (adrenal cortical adenoma (ACA): 115, adrenal cortical carcinoma (ACC): 17, and pheochromocytoma (PCC): 189). Immunohistochemical staining was performed for beclin-1, p62, LC3A, and LC3B, and the results were compared with the patients’ clinicopathologic parameters. LC3A, LC3B, beclin-1, and LC3B isolated single positive cells (ISPC) positivity rates were higher in PCC than in adrenal cortical tumor (ACT), whereas p62 positivity was lower in PCC than in ACT. The proportion of positive LC3B (ISPC) was higher in ACC than in ACA. In addition, the proportion of cells positive for p62 and LC3B (ISPC) was significantly higher in PCCs with a GAPP score of ≥3. In univariate Cox analysis, p62 positivity (p = 0.014) and the presence of p62 (ISPC) (p = 0.001) were associated with shorter disease-free survival in PCC. Moreover, p62 positivity was predictive of shorter overall survival (OS) in patients with PCC by multivariate analysis (relative risk, 6.240; 95% CI, 1.434–27.15; p = 0.015). Differences were found in the expression of autophagy-related proteins according to adrenal gland tumor types. Compared to ACT, the proportion of LC3A, LC3B, beclin-1, and LC3B (ISPC) positivity was higher in PCC, whereas p62 positivity was lower. Similarly, p62 positivity in PCC was associated with patient prognosis of OS.

Highlights

Adrenal gland tumors are typically categorized into adrenal cortical tumors (ACTs), originating from the adrenal cortex, and pheochromocytomas (PCCs), which occur in the adrenal medulla
Factors included in the Weiss system were significantly different between adrenal cortical adenoma (ACA) and adrenal cortical carcinoma (ACC)
We found that, compared to ACT, the proportion of cells positive for beclin1, LC3A, LC3B, and LC3B (ISPC) was higher in PCC, whereas p62 positivity was lower in PCC

Summary

Introduction

Adrenal gland tumors are typically categorized into adrenal cortical tumors (ACTs), originating from the adrenal cortex, and pheochromocytomas (PCCs), which occur in the adrenal medulla. In the case of high-grade malignant tumors that are characterized by increased metabolic demand, angiogenesis and/or aerobic glycolysis alone may not be able to meet the metabolic demand of tumor cells. In these circumstances, malignant cells derive energy by recycling cytoplasmic components through autophagy as an alternative [15,16]. Autophagy can theoretically contribute to both tumor progression and suppression; there is a lack of detailed research about the expression of autophagy-related proteins in adrenal gland tumors. The aim of this study was to investigate the expression and implication of key autophagy components, LC3A, LC3B, beclin-1, and p62, in human adrenal gland tumors

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