Estrogen Receptor α and Progesterone Receptor Expression in Ovarian Adult Granulosa Cell Tumors and Sertoli-Leydig Cell Tumors

The biologic role that estrogen receptor (ER) and progesterone receptor (PR) play in ovarian sex cord-stromal tumors is poorly understood. Furthermore, immunohistochemical data on these hormone receptors in this group of neoplasms are limited and conflicting, with many reports suggesting that expression of ERalpha and/or PR is either infrequent or present at low levels in granulosa and Sertoli cell tumors. Immunohistochemical staining for ERalpha and PR was performed in 69 ovarian sex cord-stromal tumors: 41 adult granulosa cell tumors and 28 Sertoli-Leydig cell tumors. Extent of expression was scored based on the percentage of positive cells: 0, 5% or less; 1+, 6% to 25%; 2+, 26% to 50%; 3+, 51% to 75%; and 4+, 76% to 100%. Estrogen receptor alpha and PR were frequently expressed in adult granulosa cell tumors (66% and 98%, respectively) and Sertoli-Leydig cell tumors (79% and 86%, respectively). Diffuse (3+ or 4+) expression of PR was more common in adult granulosa cell tumors (68% vs. 36%; P = 0.013), whereas diffuse (3+ or 4+) expression of ERalpha was more frequent in Sertoli-Leydig cell tumors (50% vs. 20%; P = 0.010). In cases positive for both markers, adult granulosa cell tumors exhibited a focal (1+ or 2+) ERalpha/diffuse (3+ or 4+) PR coordinate profile more commonly than Sertoli-Leydig cell tumors (52% vs. 18%; P = 0.02), whereas Sertoli-Leydig cell tumors displayed a diffuse (3+ or 4+) ERalpha/focal (1+ or 2+) PR profile more frequently than adult granulosa cell tumors (36% vs. 0%; P = 0.0007). We conclude that expression of hormone receptors (based only on frequency of immunostaining) does not allow for distinction from other tumors in the differential diagnosis that are known to be frequently positive for ERalpha and PR such as endometrioid neoplasms. Most adult granulosa cell tumors and Sertoli-Leydig cell tumors share overlapping patterns of expression of ERalpha and PR with each other, but a subset of cases in each tumor category exhibits unique ERalpha/PR immunoprofiles (eg, focal ERalpha/diffuse PR in adult granulosa cell tumors and diffuse ERalpha/focal PR in Sertoli-Leydig cell tumors). These patterns of expression of ERalpha and PR may aid our understanding of the biologic differences between granulosa and Sertoli cell tumors.