Abstract: TH-PO198
Differential C-X-C Motif Chemokine Receptor 4 (CXCR4) Expression in Aldosterone-Producing vs. Nonfunctional Adenomas
Session Information
- Hypertension and CVD: Basic Research Findings
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Author
- Wu, Chunyi, University of Michigan, Ann Arbor, United States
Group or Team Name
- Molecular and Integrative Physiology and Internal Medicine, University of Michigan.
Background
Primary aldosteronism (PA) is the leading cause of secondary hypertension and may have detrimental renal consequences. Unilateral PA can be cured with adrenalectomy. However, subtyping into unilateral or bilateral disease can be costly, invasive, and clinically challenging. Aldosterone-producing adenoma (APA)-targeted positron emission tomography/computed tomography (PET/CT) has emerged as a potential non-invasive imaging technique for subtype determination that could circumvent the need for gold standard adrenal venous sampling (AVS). Radiolabeled probes have been developed that bind the enzyme aldosterone synthase (CYP11B2) and chemokine receptor 4 (CXCR4). However, the expression of CXCR4 in APA and non-functional adenomas (NFA) has not been extensively studied.
Objective: To evaluate the differential expression of CXCR4 in APA versus NFA, thereby assessing its viability as a reliable biomarker in PET/CT imaging for PA subtyping.
Methods
A cohort of twenty PA patients who underwent unilateral adrenalectomy that were found to have an APA and an adjacent NFA from the university of Michigan were included in this study. Formalin-fixed, paraffin-embedded (FFPE) sections of resected adrenal tissue were used for the analysis. Aldosterone synthase (CYP11B2) immunohistochemistry (IHC) was performed to identify APA (CYP11B2 positive) and NFA (CYP11B2 negative). APA and NFA RNA was isolated followed by quantitative RT-PCR (qPCR) for ACTB (β-actin), CYP11B2, and CXCR4.
Results
In APA the average fold increase of CYP11B2 mRNA relative to the adjacent NFA was 2726(± 323) (P<0.001). For CXCR4 the average fold increase of APA relative to the adjacent NFA was 2.23(±0.83) (P=0.03). Although APA CXCR4 mRNA expression did reach statistical significance compared to NFA, 3 of 20 patients had higher CXCR4 transcript levels in the adjacent NFA.
Conclusion
Our finding confirm CYP11B2 expression as a robust APA marker with significantly lower levels observed in NFA. The transcript analysis of CXCR4, however, raises concerns of its utility as a marker for APA over NFA. Additional studies are needed to examine CXCR4 protein levels in APA versus NFA to ensure specificity of CXCR4 as an APA marker in PET/CT imaging modalities.