Clinicopathologic, immunohistochemical, and molecular correlates in resected primary adrenocortical carcinoma: a single-institution cohort study

Abstract Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with heterogeneous outcomes after resection. We conducted a retrospective single-institution cohort study of 65 resected primary ACCs from 2010 to 2025. Clinicopathologic features, tumor-type-specific histologic scoring, immunohistochemistry for p53, β-catenin, and Ki-67, clinical molecular testing results, and outcomes were analyzed. Survival was evaluated using Kaplan–Meier methods and Cox models adjusted for pT category. Increased mitotic activity (> 5 mitoses per 50 high-power fields) was present in 41/55 tumors (74.5%). Clinical molecular testing was performed in 32 tumors; 12 (37.5%) had at least one pathogenic or likely pathogenic (P/LP) alteration, most commonly involving TP53 (6/12) and CTNNB1 (3/12). P/LP alteration positivity was associated with worse overall survival (OS) after pT adjustment (HR, 4.67; 95% CI, 1.26–17.26; p = 0.021). Nuclear β-catenin expression was also associated with worse OS after pT adjustment (HR, 3.23; 95% CI, 1.19–8.79; p = 0.022). Increased mitotic activity remained associated with worse OS after pT adjustment (HR, 4.62; 95% CI, 1.07–19.91; p = 0.040), whereas its association with disease-specific survival did not reach statistical significance after pT adjustment (HR, 7.44; 95% CI, 0.98–56.21; p = 0.052). Ki-67 ≥ 10%, aberrant p53 staining, tumor necrosis, and angioinvasion were not significantly associated with survival after pT adjustment. Oncocytic ACCs had less frequent increased mitotic activity than conventional ACCs (44.4% vs. 79.1%; p = 0.048). Mitotic activity, nuclear β-catenin expression, and clinically reported P/LP alterations may provide complementary prognostic information in resected primary ACC. Larger cohorts with standardized pathology review and uniform molecular profiling are needed.