Mutational analysis of FOXL2 p.C134W and expression of bone morphogenetic protein 2 in Japanese patients with granulosa cell tumor of ovary

J Obstet Gynaecol Res. 2014 May;40(5):1197-204. doi: 10.1111/jog.12324. Epub 2014 Apr 2.

Abstract

Aim: 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.

Conclusion: 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.

Keywords: bone morphogenetic protein 2; follistatin; granulosa cell tumor; inhibin; ovarian tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bone Morphogenetic Protein 2 / analysis*
  • Female
  • Forkhead Box Protein L2
  • Forkhead Transcription Factors / genetics*
  • Granulosa Cell Tumor / chemistry
  • Granulosa Cell Tumor / genetics*
  • Humans
  • Immunohistochemistry
  • Mutation*
  • Ovarian Neoplasms / chemistry
  • Ovarian Neoplasms / genetics*

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • FOXL2 protein, human
  • Forkhead Box Protein L2
  • Forkhead Transcription Factors