FOXL2 – A Novel Marker for Granulosa Cell Tumors
M Ivanovic, E Lengyel, A Montag, K Gwin. University of Chicago, Chicago, IL
Background: FOXL2, a member of the forkhead-winged-helix family of transcription factors, is one of the earliest expressed genes during the development of the female gonad and is required for proper differentiation of granulosa cells (GC) during folliculogenesis. FOXL2 expression persists into adulthood. We hypothesized that FOXL2 could be a useful marker for granulosa cell differentiation in morphologic challenging cases.
Design: Paraffin embedded material of 38 granulosa (adult type =37, juvenile type =1) cell tumors (GCT) and 30 non-granulosa cell tumors (non-GCT) of the ovary were used to construct tissue microarrays (TMA). The control group of the non-granulosa cell tumors included various subtypes of sex cord-stromal tumors (other than GC), epithelial, germ cell and mixed germ cell-sex cord-stromal tumors. FOXL2 expression was evaluated by IHC for localization and intensity of immunoreactivity. Staining intensity was divided into three groups: no staining, low intensity staining and high intensity staining.
Results: All thirty-eight cases of GCT stained positive for FOXL2. 92% (35 cases) showed high-intensity staining and 8% (3 cases) showed low-intensity staining. In the control group of non-GCT tumors, 63.3% (19 cases) were negative for FOXL2, and 23.3% (7 cases) revealed low-intensity staining. Only 13.3%, 4 cases (one of each: fibrothecoma, thecoma,fibroma, and gonadoblastoma) exhibited high-intensity staining. In gonadoblastoma, only the sex cord derivatives exhibited staining. None of epithelial tumors stained positive for FOXL2.
Conclusions: All granulosa cell tumors exhibited immunoreavity for FOXL2, with 92% showing strong immunoreactivity. In contrast, the control group was mostly negative or revealed only weak staining. In addition, the sex cord derivatives resembling immature granulosa-cells of a gonadoblastoma expressed FOXL2. Our findings support that FOXL2 is a very useful marker to identify granulosa cell differentiation in ovarian tumors. This may be helpful in the differential diagnosis of the sex cord-stromal tumors group, especially between granulosa cell tumor and Sertoli cell tumor, that often display overlapping morphologic features.
Category: Gynecologic & Obstetrics
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 170, Wednesday Afternoon