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The FOXL2 mutation (c.402C>G) in adult-type ovarian granulosa cell tumors of three Japanese patients: clinical report and review of the literature.

Adult-type granulosa cell tumor (AGCT) is a rare class of malignant ovarian tumor with unique features, characterized by slow growth, late recurrence, relatively good prognosis and unified cause in almost all patients. The forkhead box L2 (FOXL2) gene encodes an essential transcription factor in the ovary. FOXL2 is important in female sex determination, follicle recruitment, and granulosa cell development. About 70-97% of AGCTs were reported to carry a somatic mutation c.402C>G (C134W) in the FOXL2 gene. However, it is unknown whether AGCTs of Japanese patients harbor the FOXL2 c.402C>G mutation. Here, we report a mutational analysis of the FOXL2 gene in four Japanese patients with AGCTs, and we review the literature to determine the precise incidence of FOXL2 mutations in AGCTs. All four patients were analyzed by immunohistochemistry for FOXL2. Genomic DNA was extracted from paraffin-embedded tissues, and was analyzed to detect the c.402C>G mutation in FOXL2 by direct sequencing. All tumors were stained with FOXL2. Three of the four tumors harbor the c.402C>G mutation. Based on the literature review, FOXL2 immunostaining is a highly specific marker for sex cord-stromal tumors (SCSTs), but it is not specific for AGCTs, one subtype of SCSTs. We identified 340 patients with the FOXL2 mutation (c.402C>G) and determined that the incidence of the mutation is 91.9% in AGCT patients. Therefore, this FOXL2 mutation is specific to AGCTs in the ovary and is useful for diagnosis of this disease.