Expression of SOAT1 in adrenocortical carcinoma and response to mitotane monotherapy: an ENSAT multicenter study

Isabel Weigand, Barbara Altieri, Amanda Lacombe, Vittoria Basile, Stefan Kircher, Laura-Sophie Landwehr, Jochen Schreiner, Maria Zerbini, Cristina Ronchi, Felix Megerle, Alfredo Berruti, Letizia Canu, Marco Volante, Isabel Paiva, Silvia Della Casa, Silviu Sbiera, Martin Fassnacht, Maria Fragoso, Massimo Terzolo, Matthias Kroiss

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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: 231 ACC patients treated with single agent mitotane as adjuvant (n=158) or advanced disease therapy (n=73) from twelve ENSAT centers were included. SOAT1 protein expression was determined by immunohistochemistry on formalin-fixed paraffin-embedded (FFPE) specimens.

Setting: Retrospective study at 12 ACC referral centers

Main outcome measure: recurrence-free survival (RFS), progression-free survival (PFS), disease-specific survival (DSS)

Results: 61/135 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, tumour stage and Ki67 index, RFS (HR=1.07, 95% 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.
Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Early online date25 May 2020
DOIs
Publication statusE-pub ahead of print - 25 May 2020

Keywords

  • adrenal cancer
  • chemotherapy
  • treatment
  • prognosis

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