7974 Expression of C-X-C Motif Chemokine Receptor 4 (CXCR4) in Aldosterone-Producing Adenomas and Adjacent Non-Functional Adenomas

Disclosure: C. Wu: None. K. Nanba: Grant Recipient; Self; AstraZeneca. A. Blinder: None. J.M. Luther: None. A. Turcu: None. T.J. Giordano: None. A. Udager: None. W.E. Rainey: None. Background: Primary aldosteronism (PA) is the leading cause of endocrine hypertension, and when unilateral, it can be cured with adrenalectomy. 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 that could circumvent the need for adrenal venous sampling (AVS) for subtype determination. 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 utility as a reliable biomarker in PET/CT imaging for PA subtyping. Methods: A cohort of twenty-one patients with PA who underwent unilateral adrenalectomy and were found to have an APA and an adjacent NFA 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: Compared to the adjacent NFA, APA expressed 1108 ±370-fold more CYP11B2 (P=0.007). For CXCR4 the average fold increase of APA relative to the adjacent NFA was 2.41 ±0.72 (P=0.059). Not only did APA CXCR4 mRNA expression not reach statistical significance compared to NFA, 8 of 21 patients had higher CXCR4 transcript levels in the adjacent NFA than in APA. Conclusions: Our findings confirm CYP11B2 expression as a robust and specific APA marker with low levels observed in NFA. The transcript analysis of CXCR4, however, questions its utility as a selective marker for APA over NFA. Additional studies are needed to examine the CXCR4 protein expression in APA versus other adrenal tumors to ensure specificity of CXCR4 as an APA marker in PET/CT imaging modalities. Presentation: 6/3/2024