Yanagida Satoshi, Anglesio Michael S, Nazeran Tayyebeh M, Lum Amy, Inoue Momoko, Iida Yasushi, Takano Hirokuni, Nikaido Takashi, Okamoto Aikou, Huntsman David G
Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
PLoS One. 2017 Jun 8;12(6):e0178989. doi: 10.1371/journal.pone.0178989. eCollection 2017.
Adult-type granulosa cell tumors of the ovary (aGCTs) are rare tumors that represent 2-5% of ovarian malignancies. The prognosis of this tumor is favorable, and it is characterized by slow progression. 10-30% of these tumors recur after 4-7 years of the primary surgery and the 5-year survival rate from the first recurrence is 55%, for the incompletely resected patients. At this time, complete resection is the only prognostic factor for better outcome, and establishing a novel strategy for identification and/or treatment of recurrent tumors is crucial. After the discovery of heterozygous c.402C>G FOXL2 mutations in 97% of cases of aGCT, much effort has been made to find the role of the mutation on the pathogenesis of aGCT, however, little is known about the role of the mutation in disease progression.
We analyzed the clinical data of 56 aGCT patients to find a marker of recurrence. In particular, we compared the FOXL2 status in 5 matched primary and recurrent samples by immunohistochemistry, and TaqMan allelic discrimination assay to address the role of FOXL2 in potential mechanisms of recurrence.
The clinical data analysis was consistent with complete resection as an indicator of disease eradication, though the sample size was limited. The genetic analysis showed all the samples, including recurrent tumor samples up to 14 years after the primary surgery, expressed heterozygous c.402C>G FOXL2 mutation and the FOXL2 protein expression.
This report describes the preservation of heterozygous c.402C>G FOXL2 mutation in recurrent aGCTs. This finding adds further credence to the concept that the c.402C>G FOXL2 mutation is oncogenic and integral to this disease.
成人型卵巢颗粒细胞瘤（aGCTs）是罕见肿瘤，占卵巢恶性肿瘤的2%-5%。该肿瘤预后良好，其特点是进展缓慢。这些肿瘤中有10%-30%在初次手术后4-7年复发，对于未完全切除的患者，首次复发后的5年生存率为55%。此时，完整切除是获得更好预后的唯一预后因素，建立一种识别和/或治疗复发性肿瘤的新策略至关重要。在97%的aGCT病例中发现杂合性c.402C>G FOXL2突变后，人们为寻找该突变在aGCT发病机制中的作用付出了很多努力，然而，关于该突变在疾病进展中的作用知之甚少。
我们分析了56例aGCT患者的临床数据以寻找复发标志物。特别是，我们通过免疫组织化学和TaqMan等位基因鉴别分析比较了5对匹配的原发和复发样本中的FOXL2状态，以探讨FOXL2在潜在复发机制中的作用。
尽管样本量有限，但临床数据分析与完整切除作为疾病根除指标的结果一致。基因分析显示，所有样本，包括初次手术后长达14年的复发肿瘤样本，均表达杂合性c.402C>G FOXL2突变和FOXL2蛋白表达。
本报告描述了复发性aGCT中杂合性c.402C>G FOXL2突变的保留情况。这一发现进一步支持了c.402C>G FOXL2突变具有致癌性且是该疾病不可或缺的这一概念。
