91P - Molecular predictors of response to the therapy with mitotane in adrenocortical cancer

Background

Adrenocortical cancer (ACC) therapy is characterized by insufficient effectiveness. Currently, mitotane, an adrenolytic drug, is the only drug approved for treatment of ACC and is used in the adjuvant setting and in case of metastatic or advanced disease. However, the administration of mitotane to certain groups of patients remains controversial due to the low response rates, high toxicity and limited data on the benefit of treatment. Expression levels of the large subunit of ribonucleotide reductase M1 (RRM1), cytochrome P450 2W1 (CYP2W1) and sterol-O-acyltransferase-1 (SOAT1) are considered as potential predictors of response to mitotane therapy. The aim of this study was to estimate the immunohistochemical expression of RRM1, CYP2W1 and SOAT1 in ACC as markers of clinical outcomes and response to the therapy with mitotane.

Methods

The study included 62 patients older than 17 years of age with a diagnosis of ACC confirmed histologically and immunohistochemically. Pathomorphological examination of surgical and consultative material from patients treated between 2005 and 2020 in Endocrinology research center and other health care centers of Russia was performed. Antibodies to SF-1, Ki-67, RRM1, CYP2W1, SOAT1 were used diluted in accordance with recommendations of firms-manufacturers for immunohistochemical detection. Kaplan-Meier method was used to estimate disease-free survival (DFS) and its predictors.

Results

Mitotane therapy was initiated in 29 patients in the postoperative period, the control group comprised 33 patients according to results of immunohistochemical examination (level of expression of Ki-67). In the control group of patients with low and moderate RRM1, CYP2W1 and SOAT1 immunoreactivity, a better DFS was observed (p=0.037, p=0.020 and p=0.001, respectively) compared to the study group at this level of marker expression. In case of high expression levels of the markers, no statistically significant differences were found.

Conclusions

In this study we have identified tendences in the correlation of the expression of potential prognostic markers and DFS in our sample of patients. Evaluation of RRM1, SOAT1 and CYP2W1 immunoreactivity opens new possibilities for personalized mitotane therapy in ACC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Endocrinology Research Center, Moscow, Russia.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.