Adult Granulosa Cell Tumor: Mutation Detection of FOXL2 C134W

Adult-type granulosa cell tumors (AGCTs) account for approximately 90% of malignant ovarian-sex cord stromal tumors (SCSTs) and represent 2-5% of ovarian cancers [1]. Metastasis and aggressive recurrence is associated with a poor prognosis with 80% of patients succumbing to the disease [2]. Current Scientific literature identifies FOXL2 p.C134W mutation in at least 95% of AGCTs of the ovary [1]. Currently the only diagnostic assay available for this requires extraction of DNA from tissues with subsequent sequencing. Very few laboratories offer this assay and thus a more accessible assay for determining mutation status is needed. The purpose of this study is to determine the utility of a mutation specific probe to use as a diagnostic BaseScope assay as to detect ovarian AGCTs. 69 ovarian tumors including 41 AGCTs and 28 non-AGCTs were identified in the pathology database at Stanford hospital. Non- AGCT cases were used as negative controls and included 15 benign non-AGCT SCST and 13 epithelial tumors. BaseScope-ISH assays were used to detect the mutation status of FOXL2 C134W in tissue microarrays and a subset of whole sections following guidelines (BaseScopeTM Detection Reagent Kit-RED User Manual) provided by the supplier. Samples were scored as “positive” or “negative” for FOXL2 C134W mutation status and calculations for sensitivity and specificity were performed. Based on this study, Basescope-ISH assay demonstrates 97.6% sensitivity and 100% specificity. The positive results were notably stronger in intensity in those samples <10 years old. Weak positive signals were generally associated with samples that were > 10 years old. This could be attributable to degradation of the sample over time. Nevertheless, this study suggests that the BaseScope-ISH assay with a mutation specific FOXL2 probe is an affordable and efficient tool in the diagnosis of AGCT.