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

Authors
 Hye Min Kim  ;  Ja Seung Koo 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.22(19) : 10490, 2021-09 
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Issue Date
2021-09
MeSH
Adrenal Cortex Neoplasms* / metabolism ; Adrenal Cortex Neoplasms* / mortality ; Adrenal Cortex Neoplasms* / pathology ; Adult ; Autophagy-Related Proteins / biosynthesis* ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic* ; Humans ; Male ; Middle Aged ; Neoplasm Proteins / biosynthesis* ; Pheochromocytoma* / metabolism ; Pheochromocytoma* / mortality ; Pheochromocytoma* / pathology ; Survival Rate
Keywords
adrenal gland tumor ; autophagy ; pathology ; stroma ; subtype
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.
DOI
10.3390/ijms221910490
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Koo, Ja Seung(구자승) ORCID logo https://orcid.org/0000-0003-4546-4709
Kim, Hye Min(김혜민) ORCID logo https://orcid.org/0000-0002-2899-9480
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/185950
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