Predicting recurrence in adult granulosa cell tumors: the role of Ki67, p53, and TERT mutations

Abstract

Purpose: Adult granulosa cell tumors (aGCTs) are a rare type of ovarian malignancy. While most aGCTs have an indolent course, up to 25% experience recurrence. Identifying markers for disease recurrence is crucial for optimal management. Methods: Our study consisted of a total of 55 patients, comprising primary non-recurrent aGCTs (n = 30), aGCT recurrences without corresponding primary tumors (n = 19), and primary aGCTs which later recurred along with their matched recurrences (n = 6). Immunohistochemical analysis was conducted for CD73, Ki67, and p53, along with TERT mutation analysis on selected tissue samples. Results: Immunohistochemical analysis revealed higher Ki67 proliferation index in recurrent aGCTs compared to non-recurrent cases. Mutational p53 staining was only present in recurrent cases. CD73 expression did not differ significantly between primary non-recurrent and recurrent aGCTs. A notably increased occurrence of TERT promoter mutations was identified in recurrent aGCTs (14/25, 56%) in contrast to primary non-recurrent instances (8/27, 29.6%) (p = 0.05). In primary non-recurrent aGCTs with identified TERT mutations, the C250T locus was impacted in 2 cases, while the C228T locus was affected in 6 cases. Recurrent aGCT cases predominantly exhibited TERT C228T mutation in 13 out of 14 patients. Among the six pairs of primary and recurrent aGCTs studied, four pairs displayed TERT mutations in both primary and recurrence samples. Moreover, cases with TERT mutations exhibited a higher Ki67 index. Conclusion: Identifying patients with high Ki67 and mutational p53 together with TERT mutations may help predict potential recurrence in aGCT cases. © 2025 Elsevier B.V., All rights reserved.