title: Pathogenesis and treatment of adult-type granulosa cell tumor of the ovary.
abstract: Adult-type granulosa cell tumor is a clinically and molecularly unique subtype of ovarian cancer. These tumors originate from the sex cord stromal cells of the ovary and represent 3-5% of all ovarian cancers. The majority of adult-type granulosa cell tumors are diagnosed at an early stage with an indolent prognosis. Surgery is the cornerstone for the treatment of both primary and relapsed tumor, while chemotherapy is applied only for advanced or non-resectable cases. Tumor stage is the only factor consistently associated with prognosis. However, every third of the patients relapse, typically in 4-7 years from diagnosis, leading to death in 50% of these patients. Anti-Müllerian Hormone and inhibin B are currently the most accurate circulating biomarkers. Adult-type granulosa cell tumors are molecularly characterized by a pathognomonic somatic missense point mutation 402C->G (C134W) in the transcription factor FOXL2. The FOXL2 402C->G mutation leads to increased proliferation and survival of granulosa cells, and promotes hormonal changes. Histological diagnosis of adult-type granulosa cell tumor is challenging, therefore testing for the FOXL2 mutation is crucial for differential diagnosis. Large international collaborations utilizing molecularly defined cohorts are essential to improve and validate new treatment strategies for patients with high-risk or relapsed adult-type granulosa cell tumor. Key Messages: Adult-type granulosa cell tumor is a unique ovarian cancer with an indolent, albeit unpredictable disease course. Adult-type granulosa cell tumors harbor a pathognomonic somatic missense mutation in transcription factor FOXL2. The key challenges in the treatment of patients with adult-type granulosa cell tumor lie in the identification and management of patients with high-risk or relapsed disease.
authors.affiliation: a Department of Obstetrics and Gynecology , University of Helsinki and Helsinki University Hospital , Helsinki , Finland.|b Children's Hospital , University of Helsinki and Helsinki University Hospital , Helsinki , Finland.
authors.forename: Anniina
authors.initials: A
authors.lastname: Färkkilä
authors.affiliation: a Department of Obstetrics and Gynecology , University of Helsinki and Helsinki University Hospital , Helsinki , Finland.|b Children's Hospital , University of Helsinki and Helsinki University Hospital , Helsinki , Finland.
authors.forename: Ulla-Maija
authors.initials: UM
authors.lastname: Haltia
authors.affiliation: a Department of Obstetrics and Gynecology , University of Helsinki and Helsinki University Hospital , Helsinki , Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Tapper
authors.affiliation: c Department of Human Genetics , Research Institute of the McGill University Health Centre, McGill University , Montreal , Canada.
authors.forename: Melissa K
authors.initials: MK
authors.lastname: McConechy
authors.affiliation: d Department of Pathology and Laboratory Medicine , University of British Columbia , Vancouver , Canada.|e Department of Molecular Oncology , British Columbia Cancer Agency , Vancouver , Canada.
authors.forename: David G
authors.initials: DG
authors.lastname: Huntsman
authors.affiliation: b Children's Hospital , University of Helsinki and Helsinki University Hospital , Helsinki , Finland.|f Department of Pediatrics , Washington University School of Medicine, St. Louis Children's Hospital , St. Louis , MO , USA.
authors.forename: Markku
authors.initials: M
authors.lastname: Heikinheimo
mesh_terms: D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D005260:Female; D000074842:Forkhead Box Protein L2 / Q000235:genetics*; D006106:Granulosa Cell Tumor / Q000097:blood / Q000235:genetics*; D006801:Humans; D007265:Inhibins / Q000097:blood; D020125:Mutation, Missense; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000235:genetics; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; C422364:inhibin B; D007265:Inhibins; D054304:Anti-Mullerian Hormone
keywords: Adult-type granulosa cell tumor; FOXL2; follow-up; ovarian cancer; prognostic factors; treatment