title: Mutational analysis of FOXL2 p.C134W and expression of bone morphogenetic protein 2 in Japanese patients with granulosa cell tumor of ovary.
abstract: OBJECTIVE
  To assess whether FOXL2 p.C134W mutation may play a role in the development of human ovarian tumors in the Japanese, we investigated the FOXL2 codon 134 mutation and protein expression of inhibin-α, bone morphogenetic protein 2 (BMP2) and follistatin (FST) in Japanese patients with granulosa cell tumor (GCT) of the ovary and other ovarian tumors.
  
  
  METHODS
  We analyzed 114 tumor tissues from ovarian tumors, including 44 adult-type and two juvenile-type GCT of the ovary and 68 ovarian tumors by DNA sequencing. Immunohistochemistry was also performed in the adult and juvenile GCT tissues by immunostaining inhibin-α, BMP2 and FST.
  
  
  RESULTS
  We found the FOXL2 p.C134W mutation in 27 out of 44 (61.4%) adult-type GCT of the ovary, but none in other ovarian tumors. Histologically, all of the adult-type GCT sections were positive for inhibin-α, and the expression of BMP2 and FST was detected in 14 of 44 (31.8%) and zero of 47 (0%), respectively. No significant differences regarding the diagnosed age, preoperative serum carbohydrate antigen 125 levels, or BMP2 immunopositivity between the FOXL2 p.C134W mutation-positive and mutation-negative were found in the adult-type GCT patients.
  
  
  CONCLUSIONS
  Our findings suggest that FOXL2 p.C134W mutation-positive adult-type GCT of the ovary may not be common in the Japanese as compared to the previous data.
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Oseto
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Suzumori
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Nishikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Arakawa
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ozaki
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Asai
authors.forename: Michiyasu
authors.initials: M
authors.lastname: Kawai
authors.forename: Kimio
authors.initials: K
authors.lastname: Mizuno
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirai
authors.forename: Chisato
authors.initials: C
authors.lastname: Yamada-Namikawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakanishi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kajiyama
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kikkawa
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sugiura-Ogasawara
mesh_terms: D000328:Adult; D055396:Bone Morphogenetic Protein 2 / Q000032:analysis*; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006106:Granulosa Cell Tumor / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000235:genetics*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors
keywords: bone morphogenetic protein 2; follistatin; granulosa cell tumor; inhibin; ovarian tumor