FOXL2 mutation was present in 44 out of 47 adult granulosa cell tumors (94%), in 3 out of 8 Thecomas (37%), in 1 out of 10 Sertoli-Leydig cell tumors (SLSTs) (10%) and in 3 out of 5 undifferentiated-SCSTs (Und-SCSTs) (60%).
FOXL2 mutation analysis is a useful adjunct in distinguishing between diffuse adult granulosa cell tumor (mutation present) and cellular fibroma (mutation absent).
Overexpression of wild-type but not C134W mutant FOXL2 enhances GnRH-induced cell apoptosis by increasing GnRH receptor expression in human granulosa cell tumors.
Recently, a single point missense mutation (C134W) was found in the FOXL2 gene in approximately 95% of adult-type granulosa cell tumors, suggesting a key role for FOXL2 in these tumors.
Conversely, 3 cases with an original diagnosis of granulosa cell tumor were FOXL2 mutation-negative, and none of 7 tumors with satisfactory analysis demonstrated a DICER1 mutation.
FOXL2 immunostaining was present in 95 of 119 (80%) SCSTs, including >95% of aGCTs, juvenile granulosa cell tumors, fibromas, and sclerosing stromal tumors.
We also found that the mutated tumors had a higher immunohistochemical expression of the FOXL2 protein, and there was a linear correlation between mRNA and immunohistochemical FOXL2 expression in both adult and juvenile granulosa cell tumors.
Mutational analysis (c.402C>G) of the FOXL2 gene and immunohistochemical expression of the FOXL2 protein in testicular adult type granulosa cell tumors and incompletely differentiated sex cord stromal tumors.
Recently, FOXL2 c.402C>G, a new somatic mutation that leads to a p.C134W change, was found in the majority of adult-type ovarian granulosa cell tumors (GCTs).
We undertook this study to verify the presence of the FOXL2Cys134Trp mutation in two geographically independent cohorts of granulosa cell tumors and to examine the expression pattern of FOXL2 in these tumors.
Recently, a new mutation in FOXL2, c.402C→G leading to a p.C134W change, was reported to be found in 97% of adult-type ovarian granulosa cell tumors (GCTs) tested.
Recently, we reported the identification of a somatic FOXL2 402C-->G mutation that is present in virtually all adult-type granulosa cell tumors, but not in a wide range of other tumor types.
In addition to proving that the KGN cell line is a useful model to study A-GCTs, these data show that the c.402C>G mutation in FOXL2 is not commonly found in a wide variety of other cancers and therefore it is likely pathognomonic for A-GCTs and closely related tumors.
We evaluated four patients with ovarian juvenile granulosa cell tumors (age range, 2.4 to 7.2; median, 2.9 years) and five healthy pubertal girls (age range, 16 to 18.5; median, 16.8 years) for activating mutations in exon 10 of the FSHR.