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Updated: Aug 18, 2026

A Novel Method: Super-selective Adrenal Venous Sampling
Published on: September 15, 2017
AKT is highly phosphorylated in pheochromocytomas but not in benign adrenocortical tumors
Martin Fassnacht1, Dirk Weismann, Silke Ebert
1Department of Medicine, Endocrine and Diabetes Unit, University of Würzburg, 97080 Würzburg, Germany. Fassnacht_m@medizin.uni-wuerzburg.de
Context:
Activation of AKT plays a major role in a variety of human neoplasias. In mice, a heterozygous deletion of the Pten gene is associated with increased activation of AKT and with development of pheochromocytomas.
Objective:
The objective of this study was the investigation of the role of AKT in the pathogenesis of pheochromocytomas and adrenocortical tumors.
Design, Setting, And Participants:
Total AKT and phosphorylated AKT (pAKT) in 15 pheochromocytomas, nine aldosterone-producing adenomas, nine cortisol-producing adenomas, eight adrenocortical carcinomas (ACC), and 15 normal adrenals were investigated by Western blot analysis. Immunohistochemistry for total AKT and pAKT was performed in pheochromocytomas (n = 8), ACC (n = 4), and normal adrenal glands (n = 2). In addition, in pheochromocytomas PTEN protein expression and PTEN loss of heterozygosity were analyzed.
Main Outcome Measures:
Determination of pAKT/total AKT ratio in adrenal tissues was the main outcome.
Results:
In comparison to normal adrenals, total AKT expression was elevated in both pheochromocytomas (193 +/- 22%) and ACC (176 +/- 36%). The pAKT/AKT ratio was significantly increased in pheochromocytomas (338 +/- 49% vs. 100 +/- 11%) but not in ACC, aldosterone-producing adenomas, and cortisol-producing adenomas. No loss of heterozygosity of PTEN and no decrease in PTEN protein was detected in pheochromocytomas. Immunohistochemistry showed strong and homogeneous AKT and pAKT staining in pheochromocytomas and focal staining in ACC.
Conclusion:
Our findings provide evidence for increased activation of AKT in pheochromocytomas but not in adrenocortical adenomas.
Insights
Increased AKT activation is implicated in pheochromocytomas, a finding not observed in adrenocortical adenomas. This study investigated AKT
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Activation of AKT is a significant factor in numerous human cancers.
- Pten gene heterozygous deletion in mice correlates with increased AKT activation and pheochromocytoma development.
- Understanding AKT's role is crucial for diagnosing and treating adrenal tumors.
Purpose of the Study:
- To investigate the role of AKT in the pathogenesis of pheochromocytomas.
- To examine AKT's role in the development of adrenocortical tumors.
Main Methods:
- Western blot analysis was used to quantify total AKT and phosphorylated AKT (pAKT) levels.
- Immunohistochemistry was performed to assess AKT and pAKT expression in tumor tissues.
- PTEN protein expression and loss of heterozygosity were analyzed in pheochromocytomas.
Main Results:
- Total AKT expression was elevated in pheochromocytomas and adrenocortical carcinomas (ACC) compared to normal adrenals.
- The pAKT/AKT ratio was significantly increased in pheochromocytomas but not in ACC or other adenomas.
- No PTEN loss of heterozygosity or decreased PTEN protein was found in pheochromocytomas.
Conclusions:
- Evidence suggests increased AKT activation in pheochromocytomas.
- AKT activation is not significantly increased in common adrenocortical adenomas.
- These findings differentiate the molecular pathways in pheochromocytomas versus adrenocortical adenomas.
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