Abstract
Autonomous steroid secretion is a common feature of adrenocortical carcinomas (ACC), although not always clinically evident owing to inefficient steroidogenesis with increased release of steroid precursors. Our study aim was to analyze the expression profile of four key proteins involved in the steroidogenesis cascade, in different adrenocortical tumors. 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), adenomas presenting with Cushing’s syndrome (ACAc) (n = 11) and clinically non-functioning adenomas (ACAn) (n = 15). A percentage of the stained area for each protein was analyzed using ImageJ software for computerized morphometric quantification. CYP11B1, StAR and CYP17A1 expression were significantly lower in ACC when compared to ACAc. In addition, ACC presented co-staining cells for CYP11B1 and CYP11B2. CYP11B1 was the steroidogenic enzyme with the most discriminative power to distinguish ACC from ACAc, with a sensitivity of 100%, specificity of 92%, and an expression higher than 4.44%, indicating the presence of a cortisol secreting adenoma. ACC depicts an incomplete pattern of steroidogenic protein expression, with decreased CYP11B1 and CYP17A1, which could explain the predominant secretion of steroid precursors.
Highlights
Adrenocortical carcinomas (ACC) are rare tumors and are largely associated with a poor prognosis [1]
Andandrogen observedand that a combined spectrometry in the urinespectrometry of adrenocortical tumors (ACT) patients andurine observed that apatients combined glucocorticoid androgen glucocorticoid wasACC, present inroutine
adrenocortical carcinomas (ACC), only while routine excess was and present in 69% of theexcess analyzed while analysis identified biochemistry analysis only identified of the cases
Summary
Adrenocortical carcinomas (ACC) are rare tumors and are largely associated with a poor prognosis [1]. The majority of ACC autonomously produce steroids and present as clinically functioning. Biomedicines 2020, 8, 256; doi:10.3390/biomedicines8080256 www.mdpi.com/journal/biomedicines functioning tumors in 40–60% of cases, of which 50–80% of patients exhibit Cushing’s syndrome [2–. Despite being capable of steroid production, some ACC do present without a clinically apparent hormonal syndrome. Demonstrated that the majority of patients with ACC have higher androgen and glucocorticoid. 8, 256 urinary levels when compared to patients with adrenocortical adenomas (ACA). The authors found that ACCs secrete and release predominantly intermediate metabolites, which tumors an in 40–60%. Provides explanation the absence of patients clinically apparent hormonal overproduction despite being capable of steroid production, some
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