Endocrine Abstracts

Introduction: The majority of adrenocortical carcinomas (ACC) autonomously produce steroids. However, urinary steroid profile of patients with ACC revealed that these tumors secrete and release predominantly intermediate metabolites. This steroid secretion pattern could be attributed to the undifferentiated status of the tumor cells expressing an incomplete pattern of enzymes involved in the steroidogenic cascade.

Aims: Our study aim was to analyze the expression profile of key proteins involved in the steroidogenesis cascade, in different adrenocortical tumors.

Methods: Expression of proteins involved in steroidogenesis, namely steroidogenic acute regulatory protein (StAR), 11β-hydroxylase (CYP11B1), aldosterone synthase (CYP11B2) and 17α-hydroxylase (CYP17A1), were analyzed by immunohistochemistry in ACC (n = 14), adrenocortical adenomas presenting with Cushing syndrome (ACAc) (n = 11) and non-functioning adrenocortical adenomas (ACAn) (n = 15). The percentage of the stained area for each protein was analyzed through a computerized morphometric quantification, the ImageJ software.

Results: CYP11B1, StAR and CYP17A1 expressions were significantly lower in ACC when compared to ACAc. Besides that, ACC presented co-staining cells for CYP11B1 and CYP11B2. CYP11B1 expression has a high discriminative power to distinguish ACC from ACAc with a sensitivity of 100% and specificity of 92%. CYP11B1 and CYP11B2 dual negativity presented a specificity of 100% for the differential diagnosis between ACC and ACAc.

Conclusion: ACC present an incomplete pattern of steroidogenic protein expression, with decreased CYP11B1 and CYP17A1, which could explain the predominant secretion of predominantly intermediate metabolites in ACC patients. In addition, in cortisol secreting tumors, CYP11B1 positivity alone is highly specific for benign lesions.

Funding: This study was funded by the Foundation for Science and Technology (FCT) (PTDC/MEC-ONC/31384/2017).