14-3-3 Sigma is a Useful Immunohistochemical Marker for Diagnosing Ovarian Granulosa Cell Tumors and Steroid Cell Tumors

Abstract

The distinction of ovarian granulosa cell tumors (GCTs) from other sex-cord stromal tumors may be difficult histologically. Many immunohistochemical markers have been studied for this differential diagnosis, but the available markers are not entirely specific for ovarian GCT. 14-3-3 sigma has been shown to play an anti-apoptotic role in maintaining the viability of immortalized granulosa cells. However, the potential use of this molecule as an immunohistochemical marker for the diagnosis of ovarian GCT has not been investigated. A total of 103 ovarian sex-cord stromal neoplasms were immunostained with 14-3-3 sigma. These tumors included 44 adult granulosa cell, 7 juvenile granulosa cell tumors, 12 steroid cell tumors, 3 well-differentiated Sertoli-Leydig cell tumors, 5 Sertoli cell tumors, 10 thecomas, 18 fibromas, 2 primary ovarian endometrial stromal sarcomas, and 2 unclassified sex-cord stromal tumors. Ten ovaries with cystic follicles were also included as controls. Perinuclear or cytoplasmic stain was considered to be positive. Granulosa cells within the cystic follicles were positive for 14-3-3 sigma protein. All ovarian GCT (51/51) and all steroid cell tumors (12/12) were positive for 14-3-3 sigma, and all Sertoli cell tumors, fibromas, thecomas, ovarian endometrial stromal sarcomas, and sex-cord stromal tumors, unclassified, were negative for 14-3-3 sigma. The percentage of positive cell staining is statistically significant (P<0.0001) between the above 2 groups of sex-cord stromal tumors. These findings provide the initial evidence of the overexpression of 14-3-3 sigma in granulosa cells and steroid-hormone-secreting cells. They further indicate that immunohistochemical staining of 14-3-3 sigma may be a useful marker in facilitating the diagnosis of ovarian GCT and steroid cell tumors.