Clinical and genetic analysis of recurrent adult-type granulosa cell tumor of the ovary: Persistent preservation of heterozygous c.402C>G FOXL2 mutation

PLoS One

Takashi Nikaido¹  Aikou Okamoto²  Tayyebeh M. Nazeran²  David G. Huntsman²  Yasushi Iida³  Satoshi Yanagida³  Amy Lum³  Momoko Inoue⁴  Michael S. Anglesio⁴  Hirokuni Takano⁴ 

[1] Department of Molecular Oncology, BC Cancer Agency Research Centre, Vancouver, British Columbia, Canada;Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan;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

关键词: Surgical and invasive medical procedures;    Surgical oncology;    Ovaries;    Tumor resection;    Cancer chemotherapy;    Immunohistochemistry techniques;    Cancer treatment;    Histology;   

DOI  :  10.1371/journal.pone.0178989

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Background 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. Methods 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. Results 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. Conclusion 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.

【 授权许可】

CC BY