Abstract B46: DICER1 and FOXL2 mutations correlate with clinicopathologic features of ovarian Sertoli-Leydig cell tumors

Abstract

Abstract Sertoli-Leydig cell tumors are rare mixed ovarian sex cord-stromal neoplasms consisting of a mixture of Sertoli cells, Leydig cells, and occasionally heterologous elements or retiform differentiation. The only known recurrent genetic abnormality is mutations in DICER1, with rare mutations reported in FOXL2. We set out to determine the DICER1 and FOXL2 mutation status in a series of 51 SLCTs with the goal of establishing a molecular classifier using mutation status and clinicopathologic features. Five tumors were well differentiated, 39 moderately differentiated, and 7 poorly differentiated. Nine tumors had heterologous elements (8 epithelial, one mesenchymal), and four showed retiform differentiation; all of these were moderately differentiated. DICER1 mutations were identified in 16/45 of successfully genotyped tumors (36%, 15 moderately differentiated, 1 poorly differentiated), including 7 with heterologous elements and 3 of 4 with retiform differentiation. FOXL2 c.402C>G mutation was identified in 10/51 tumors (20%, 8 moderately differentiated, 2 poorly differentiated). DICER1 and FOXL2 mutations were mutually exclusive. Median age for the entire cohort was 44 years (range 15-90). Patients with DICER1 mutations were younger (median 23.5 years, range 15-62) than patients with neither DICER1 nor FOXL2 mutation (median 41.5 years, range 16-74). Tumors with FOXL2 mutation occurred exclusively in postmenopausal patients (median 78 years, range 54-90), whereas 11/13 tumors with either heterologous elements (median 26 years, range 16-62) or retiform differentiation (median 38 years, range 18-57) occurred in premenopausal patients. Our data suggest the existence of at least three molecular subtypes of SLCT: DICER1 mutant (younger, moderately/poorly differentiated, including heterologous elements or retiform differentiation), FOXL2 mutant (postmenopausal, moderately/poorly differentiated, no heterologous elements or retiform differentiation), and DICER1/FOXL2 wild-type (no specific age, no heterologous elements, including all well-differentiated tumors). These findings suggest that well-differentiated and moderately/poorly differentiated SLCTs may be different histomolecular entities with different etiologies. Citation Format: Anthony N. Karnezis, Yemin Wang, Jamie Magrill, Jacqueline Keul, Stefan Kommoss, Basile Tessier-Cloutier, Lily Proctor, Dietmar Schmidt, C Blake Gilks, David G. Huntsman, Friedrich Kommoss. DICER1 and FOXL2 mutations correlate with clinicopathologic features of ovarian Sertoli-Leydig cell tumors. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr B46.