Abstract
Malignant adrenocortical tumors (ACTs) are rare and highly aggressive; conversely, benign tumors are common and frequently found incidentally (the so-called incidentalomas). Currently, the use of molecular markers in the diagnosis of ACTs is still controversial. The aim of this study was to analyze the molecular profile of different ACTs with the purpose of identifying markers useful for differentiating between these tumors. The ACTs that were studied (n=31) included nonfunctioning adenomas (ACAn)/incidentalomas (n=13), functioning adenomas with Cushing's syndrome (ACAc) (n=7), and carcinomas (n=11); normal adrenal glands (n=12) were used as controls. For each sample, the percentage area stained for the markers StAR, IGF2, IGF1R, p53, MDM2, p21, p27, cyclin D1, Ki-67, β-catenin, and E-cadherin was quantified using a morphometric computerized tool. IGF2, p27, cyclin D1, and Ki-67 were the markers for which the percentage of stained area was significantly higher in carcinoma samples than in adenoma samples. Ki-67 and p27 were the markers that exhibited the highest discriminative power for differential diagnosis between carcinomas and all type of adenomas, while IGF2 and StAR were only found to be useful for differentiating between carcinomas and ACAn and between carcinomas and ACAc respectively. The usefulness of Ki-67 has been recognized before in the differential diagnosis of malignant tumors. The additional use of p27 as an elective marker to distinguish benign ACTs from malignant ACTs should be considered.
Highlights
Detection of adrenal tumors has increased in the last few years due to the widespread use of imaging methods such as computerized tomography or magnetic resonance imaging (1, 2)
Incidentaloma samples exhibited staining that was lower than that exhibited by ACAc samples and similar to that exhibited by adrenocortical carcinomas (ACCs) samples
The receiver operating characteristic (ROC) curve was constructed to assess the accuracy of StAR for the differential diagnosis between ACAcs and ACCs
Summary
Detection of adrenal tumors has increased in the last few years due to the widespread use of imaging methods such as computerized tomography or magnetic resonance imaging (1, 2). Most are benign nonsecretory adrenal tumors, with a prevalence of more than 4% in the adult population; in contrast, adrenocortical carcinomas (ACCs) are rare, having an incidence of between 0.5 and 2 per million, and are generally highly aggressive, with a poor prognosis that is expressed by a 5-year survival rate of between 16 and 38% (1, 3, 4, 5). The correct diagnosis of adrenocortical tumors (ACTs) is, understandably of growing importance. Some malignant tumors secrete precursor steroids or even inactive steroids and do not produce a clinical syndrome in spite of being functioning
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