SUN-350 Sterol-O-Acyl Transferase 1 Protein Expression Alone Is Not Sufficient to Predict Response to Mitotane Treatment in Adrenocortical Carcinoma

Background: Objective response rate to mitotane in advanced ACC is only ~20% and adverse drug effects are frequent and potentially serious. Markers of treatment response are not established. We have previously discovered that mitotane is an inhibitor of sterol-O-Acyl transferase 1 (SOAT1) which leads to depletion of cholesterol esters, endoplasmic reticulum stress and cell death in the ACC cell line NCI-H295. Data from a small cohort of patients with advanced ACC treated with mitotane monotherapy suggested longer progression-free survival in patients with high SOAT1 expression in ACC tissue. Aim: To investigate SOAT1 protein expression as a marker of treatment response to mitotane. Methods: SOAT1 protein expression was semiquantitatively determined by immunohistochemistry in full sections of 223 ACC treated with mitotane monotherapy in an adjuvant (n=151) and palliative setting (n=72) from eleven ENSAT centers. Expression was classified as high (H-score ≥2) and low (H-score <2) and correlated with recurrence-free (RFS) and progression-free survival (PFS), overall survival (OS), and mitotane levels after three and six months. Results: After multivariate adjustment for sex, ENSAT stage and Ki67 index, RFS (HR=1.3, log rank p=0.09) and OS (HR=1.6, log rank p=0.14) in adjuvantly treated ACC patients did not differ significantly between tumours with high and low SOAT1 expression. Similarly in the palliative setting, OS (HR=1.0, p=0.47) and PFS (HR=0.6, p=0.66) were not different. In line, high SOAT1 expression did not predict if patients reach the therapeutic window of mitotane. Conclusion: SOAT1 expression alone was not correlated with clinically significantly RFS, PFS, and OS in ACC patients neither in the adjuvant nor in the palliative setting.