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. 2021 Sep 28;22(19):10490.
doi: 10.3390/ijms221910490.

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

Hye Min Kim  1 , Ja Seung Koo  1
Affiliations

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

Hye Min Kim et al. Int J Mol Sci. .

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.

Keywords: adrenal gland tumor; autophagy; pathology; stroma; subtype.

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Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1
Expression of autophagy-related proteins in adrenal cortical tumor and pheochromocytoma. LC3A, LC3B, beclin-1, and LC3B (ISPC) positivity rates were higher in PCC than in ACT, whereas p62 positivity was lower in PCC.
Figure 2
Figure 2
Isolated single positive cells (ISPC) of p62 and LC3B stain in adrenal tumors. The ISPC proportion of LC3B was higher in ACC than in ACA. The ISPC proportions of p62 and LC3B were significantly higher in PCCs with a GAPP score of ≥3 than in PCCs with a GAPP score of <3. Arrows indicate ISPC.
Figure 3
Figure 3
The presence/absence of clinicopathologic factors and the expression of autophagy-related proteins in adrenal cortical tumor and pheochromocytoma.
Figure 4
Figure 4
Impact of the expression of autophagy-related proteins on prognosis in pheochromocytoma. The p62 (left figure) and p62 (ISPC) (middle figure) positivity was associated with shorter disease-free survival in PCC, whereas p62 positivity was also associated with shorter overall survival (right figure).
See this image and copyright information in PMC

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