Sterol O-Acyl Transferase 1 as a Prognostic Marker of Adrenocortical Carcinoma

Author(s):Show less -

Ferreira Lacombe, Amanda Meneses ^[1] ; Soares, Ibere Cauduro ^[2] ; de Paula Mariani, Beatriz Marinho ^[1] ; Nishi, Mirian Yumie ^[1] ; Bezerra-Neto, Joao Evangelista ^[3] ; Charchar, Helaine da Silva ^[1] ; Brondani, Vania Balderrama ^[1] ; Tanno, Fabio ^[4] ; Srougi, Victor ^[4] ; Chambo, Jose Luiz ^[4] ; Costa de Freitas, Ricardo Miguel ^[5] ; Mendonca, Berenice Bilharinho ^[1] ; Hoff, Ana O. ^[6] ; Almeida, Madson Q. ^{[1, 6]} ; Weigand, Isabel ^[7] ; Kroiss, Matthias ^[7] ; Nogueira Zerbini, Maria Claudia ^[8] ; Barisson Villares Fragoso, Maria Candida ^{[1, 6]}

Affiliation

^[1] Univ Sao Paulo, Fac Med, Serv Endocrinol & Metabol, Hosp Clin, Unidade Suprarrenal, Lab Hormonios & Genet Mol LIM, Ave Dr Eneas Carvalho Aguiar 155, BR-05403900 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Fac Med, ICESP, Serv Anat Patol, Ave Dr Arnaldo 251, BR-01246000 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Fac Med, ICESP, Serv Oncol Clin, Ave Dr Arnaldo 251, BR-01246000 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Fac Med, Hosp Clin, Serv Urol, Ave Dr Eneas Carvalho Aguiar 255, BR-05403000 Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Fac Med, ICESP, Serv Radiol, Ave Dr Arnaldo 251, BR-01246000 Sao Paulo, SP - Brazil

^[6] Univ Sao Paulo, Fac Med, ICESP, Serv Endocrinol, Ave Dr Arnaldo 251, BR-01246000 Sao Paulo, SP - Brazil

^[7] Hosp Univ Wurzburg, Unidade Endocrinol & Diabet, Dept Med Interna, Josef Schneider Str, D-97080 Wurzburg - Germany

^[8] Univ Sao Paulo, Fac Med, Dept Anat Patol, Ave Dr Arnaldo 455, BR-01246903 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: CANCERS; v. 12, n. 1 JAN 2020.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 17/26345-5 - Evaluation of prognostic factors of adrenal cortex tumors and predictors of response to treatment with mitotane in carcinomas
• Grantee: Maria Candida Barisson Villares Fragoso
• Support Opportunities: Regular Research Grants