Abstract
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis. Despite the poor prognosis in the majority of patients, no improvements in treatment strategies have been achieved. Therefore, the discovery of new prognostic biomarkers is of enormous interest. Sterol-O-acyl transferase 1 (SOAT1) is involved in cholesterol esterification and lipid droplet formation. Recently, it was demonstrated that SOAT1 inhibition leads to impaired steroidogenesis and cell viability in ACC. To date, no studies have addressed the impact of SOAT1 expression on ACC prognosis and clinical outcomes. We evaluated SOAT1 expression by quantitative real-time polymerase chain reaction and immunohistochemistry in a tissue microarray of 112 ACCs (Weiss score ≥ 3) from adults treated in a single tertiary center in Brazil. Two independent pathologists evaluated the immunohistochemistry results through a semiquantitative approach (0–4). We aimed to evaluate the correlation between SOAT1 expression and clinical, biochemical and anatomopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). SOAT1 protein expression was heterogeneous in this cohort, 37.5% of the ACCs demonstrated a strong SOAT1 protein expression (score > 2), while 62.5% demonstrated a weak or absent protein expression (score ≤ 2). Strong SOAT1 protein expression correlated with features of high aggressiveness in ACC, such as excessive tumor cortisol secretion (p = 0.01), an advanced disease stage [European Network for the Study of Adrenal Tumors (ENSAT) staging system 3 and 4 (p = 0.011)] and a high Ki67 index (p = 0.002). In multivariate analysis, strong SOAT1 protein expression was an independent predictor of a reduced OS (hazard ratio (HR) 2.15, confidence interval (CI) 95% 1.26–3.66; p = 0.005) in all patients (n = 112), and a reduced RFS (HR 2.1, CI 95% 1.09–4.06; p = 0.027) in patients with localized disease at diagnosis (n = 83). Our findings demonstrated that SOAT1 protein expression has prognostic value in ACC and reinforced the importance of investigating SOAT1 as a possible therapeutic target for patients with ACC.
Highlights
IntroductionAdrenocortical carcinoma (ACC) is a rare neoplasia with an estimated incidence of
Adrenocortical carcinoma (ACC) is a rare neoplasia with an estimated incidence of0.5–2.0/million/year in adults [1,2]
The 112 cases were separated into two different groups according to ENSAT stage at diagnosis, and we evaluated the impact of Sterol-O-acyl transferase 1 (SOAT1) protein expression on progression-free survival (PFS) in the subgroup of patients with metastatic disease at diagnosis (ENSAT 4; n = 22), and on recurrence-free survival (RFS) in the subgroup of patients with localized disease at diagnosis who underwent complete surgical resection of the primary tumor (resection status R0 (n = 83))
Summary
Adrenocortical carcinoma (ACC) is a rare neoplasia with an estimated incidence of. 0.5–2.0/million/year in adults [1,2]. A significant number of patients already present with metastatic disease at diagnosis and have a median overall survival (OS) of 12–15 months and limited therapeutic options. Even after complete resection in cases of localized disease at diagnosis, ACC harbors a significant risk for recurrence and metastatic spread [2,3]; this risk is not predictable [4]. The exploration of new prognostic biomarkers with possible implications for better decision-making about how to use the available therapies and the development of new therapeutic alternatives is of great interest. SOAT1 is ubiquitously expressed in most cell types and tissues, but its highest expression is observed in adrenocortical cells (www.proteinatlas.org)
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