Abstract

Aim: Adrenocortical carcinoma (ACC) is a rare but mortal endocrine malignancy. While expression of sex steroid receptors is well-known to be associated with tumor prognosis and treatment response in a number of hormone sensitive cancers, sex steroid receptor expression in ACC is not revealed in this context. The aim of this study is to assess prognostic implications of sex steroid receptor expression in ACCs. Method: Paraffin-embedded blocks of 16 ACC cases (8 F, 8 M, mean age 47.9±13.9) and 22 benign adrenocortical adenoma (ACA) cases (14 F, 8 M, mean age 50.0±11.4) who were undergone surgery in our center between 1998-2017 were examined in this case-control study. Estrogen (ER, Leica), androgen (AR, CellMarque) and progesterone receptor (PR, Leica) expressions in both tumor and peritumoral adrenal tissue were semi-quantitatively scored by immunohistochemistry (IHC), by an endocrine pathology specialist. The relationship between the histopathological prognostic indicators, the clinical course of patients and intra-tumor and peritumoral sex steroid receptor expression status were examined. Results: ER and AR expressions of ACCs were significantly higher, while all ACAs were ER and AR negative (ER 25% vs 0%, p=0.014; AR 31% vs 0%, p=0.005). PR expression was similar between groups; although, higher rate of PR expression was observed in ACAs (75% vs 86%, p=0.38). While peri-tumoral adrenal tissue of ACC cases did not express none of the three sex steroid receptors, IHC staining of peripheral adrenal tissue of ACAs revealed positivity for ER, AR and PR (p values <0.005). ACC cases which were negative for ER, PR and/or AR had larger tumor size (r=-0.6, p=0.015). Tumor stage was more advanced in AR negative ACCs (r=-0.6, p=0.021). Progression free survival was shorter in ACC cases which were positive for PR (15 vs 57.5 months, p=0.07); while it was longer in cases peritumoral adrenal tissue was positive for either of three sex steroid receptors (r=0.81, p=0.008). Conclusions: For the first time in this study, expression of sex steroid receptors has been shown to be related with ACC prognosis and clinical/histopathological behaviour.

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