Low Protein Expression of both ATRX and ZNRF3 as Novel Negative Prognostic Markers of Adult Adrenocortical Carcinoma

Adrenocortical carcinoma (ACC) is a rare malignancy that is associated with a dismal prognosis. Pan-genomic studies have demonstrated the involvement of and genes in adrenocortical tumorigenesis. Our aims were to evaluate the protein expression of and in a cohort of 82 adults with ACC and to establish their prognostic value. Two pathologists analyzed immuno-stained slides of a tissue microarray. The low protein expression of and was associated with a decrease in overall survival (OS) ( = 0.045, = 0.012, respectively). The Cox regression for protein expression of >1.5 showed a hazard ratio (HR) for OS of 0.521 (95% CI 0.273-0.997; = 0.049) when compared with ≤1.5; for expression >2, the HR for OS was 0.441 (95% CI, 0.229-0.852; = 0.015) when compared with ≤2. High and protein expressions were associated with optimistic recurrence-free survival (RFS) ( = 0.027 and = 0.005, respectively). The Cox regression of RFS showed an HR of 0.332 (95%CI, 0.111-0.932) for expression >2.7 ( = 0.037), and an HR of 0.333 (95%CI, 0.140-0.790) for expression >2 ( = 0.013). In conclusion, low protein expression of and are negative prognostic markers of ACC; however, different cohorts should be evaluated to validate these findings.