Expression of SOAT1 in Adrenocortical Carcinoma and Response to Mitotane Monotherapy: An ENSAT Multicenter Study

Author(s):Show less -

Weigand, Isabel ^[1] ; Altieri, Barbara ^[1] ; Lacombe, Amanda M. F. ^[2] ; Basile, Vittoria ^[3] ; Kircher, Stefan ^[4] ; Landwehr, Laura-Sophie ^[1] ; Schreiner, Jochen ^[1] ; Zerbini, Maria C. N. ^[2] ; Ronchi, Cristina L. ^{[1, 5, 6]} ; Megerle, Felix ^[1] ; Berruti, Alfredo ^[7] ; Canu, Letizia ^[8] ; Volante, Marco ^[9] ; Paiva, Isabel ^{[10, 11]} ; Della Casa, Silvia ^[12] ; Sbiera, Silviu ^[1] ; Fassnacht, Martin ^{[1, 13]} ; Fragoso, V, Maria Candida B. ; Terzolo, Massimo ^[3] ; Kroiss, Matthias ^{[1, 13]}

Affiliation:Show less -

^[1] Univ Wurzburg, Univ Hosp, Dept Internal Med 1, Div Endocrinol & Diabet, D-97080 Wurzburg - Germany

^[2] V, Fac Med Univ Sao Paulo, Inst Canc Estado Sao Paulo ICESP, Hosp Clin, Dept Patol, Serv Endocrinol & Metabol, Unidade Suprarrenal, Lab Hormonios & Genet Mol LIM, BR-05403900 Sao Paulo - Brazil

^[3] Univ Turin, Dept Clin & Biol Sci, San Luigi Hosp, I-10043 Orbassano - Italy

^[4] Univ Wurzburg, Inst Pathol, D-97080 Wurzburg - Germany

^[5] Univ Birmingham, Inst Metab & Syst Res, Birmingham B15 2TT, W Midlands - England

^[6] Birmingham Hlth Partners, Ctr Endocrinol Diabet & Metab, Birmingham B15 2TT, W Midlands - England

^[7] Univ Brescia, Dept Med & Surg Specialties, Med Oncol Unit, Radiol Sci & Publ Hlth, ASST Spedali Civili, I-25123 Brescia - Italy

^[8] Univ Florence, Dept Expt & Clin Biomed Sci, Endocrinol Unit, I-50139 Florence - Italy

^[9] Univ Turin, Dept Oncol, I-10043 Turin - Italy

^[10] Ctr Hospitalar, Dept Endocrinol Diabet & Metab, Coimbra - Portugal

^[11] Univ Coimbra, Dept Endocrinol Diabet & Metab, Coimbra - Portugal

^[12] Catholic Univ, Fdn Policlin Gemelli, Div Endocrinol & Metab, I-00168 Rome - Italy

^[13] Univ Wurzburg, Comprehens Canc Ctr Mainfranken, D-97080 Wurzburg - Germany

• Document type: Journal article
• Source: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. 105, n. 8, p. 2642-2653, AUG 2020.
• Web of Science Citations: 0

Abstract

Context: Objective response rate to mitotane in advanced adrenocortical carcinoma (ACC) is approximately 20%, and adverse drug effects are frequent. To date, there is no marker established that predicts treatment response. Mitotane has been shown to inhibit sterol-O-acyl transferase 1 (SOAT1), which leads to endoplasmic reticulum stress and cell death in ACC cells. Objective: To investigate SOAT1 protein expression as a marker of treatment response to mitotane. Patients: A total of 231 ACC patients treated with single-agent mitotane as adjuvant (n = 158) or advanced disease therapy (n = 73) from 12 ENSAT centers were included. SOAT1 protein expression was determined by immunohistochemistry on formalin-fixed paraffin-embedded specimens. Setting: Retrospective study at 12 ACC referral centers. Main outcome measure: Recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). Results: Sixty-one of 135 patients (45%) with adjuvant mitotane treatment had recurrences and 45/68 patients (66%) with mitotane treatment for advanced disease had progressive disease. After multivariate adjustment for sex, age, hormone secretion, tumor stage, and Ki67 index, RFS (hazard ratio {[}HR] = 1.07; 95% confidence interval {[}CI], 0.61-1.85; P = 0.82), and DSS (HR = 1.30; 95% CI, 0.58-2.93; P = 0.53) in adjuvantly treated ACC patients did not differ significantly between tumors with high and low SOAT1 expression. Similarly, in the advanced stage setting, PFS (HR = 1.34; 95% CI, 0.63-2.84; P = 0.45) and DSS (HR = 0.72; 95% CI, 0.31-1.70; P = 0.45) were comparable and response rates not significantly different. Conclusions: SOAT1 expression was not correlated with clinical endpoints RFS, PFS, and DSS in ACC patients with mitotane monotherapy. Other factors appear to be relevant for mitotane treatment response and ACC patient survival. (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