title: Characteristics and outcome of recurrence in molecularly defined adult-type ovarian granulosa cell tumors.
abstract: OBJECTIVE
  Adult-type ovarian granulosa cell tumors (AGCTs) have an unpredictable tendency to relapse. In a carefully validated patient cohort, we evaluated the prognostic factors related to AGCT recurrence.
  
  
  METHODS
  We identified all patients diagnosed with AGCT during 1956-2014 in Helsinki University Hospital, with a minimum follow-up of one year (n=240). After a histological review supplemented with FOXL2 (402C-G) mutation status analysis, we analyzed the clinical data for association with relapse.
  
  
  RESULTS
  The final cohort included 164 (68%) molecularly defined AGCTs (MD-AGCTs). The majority of the women were postmenopausal (63%), and 92% of tumors were stage I. The median follow-up time was 15.5years. Fifty-two (32%) patients developed tumor recurrence, of whom 55% had successive recurrences. Multiple-site recurrences were common, and nearly half of the recurrences were asymptomatic. The median time to the first relapse was 7.4years, and 75% of relapses occurred within ten years after primary diagnosis. The median disease-free survival was 11.3years. Premenopausal status at initial diagnosis, FIGO stage Ic versus Ia, and tumor rupture associated with relapse. However, tumor rupture was the only independent predictive factor. Of the relapsed patients, 48% died of AGCT in a median time of 15.3years.
  
  
  CONCLUSIONS
  Tumor rupture is the strongest predictive factor for recurrence, and these patients might benefit from a more aggressive initial treatment approach. AGCT requires active follow up for 10 to 15years after primary diagnosis, since recurrences may develop late, asymptomatically and in multiple anatomical locations.
authors.affiliation: Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Finland; Children's Hospital, University of Helsinki and Helsinki University Hospital, Finland. Electronic address: saara.bryk@hus.fi.
authors.forename: Saara
authors.initials: S
authors.lastname: Bryk
authors.affiliation: Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Finland; Children's Hospital, University of Helsinki and Helsinki University Hospital, Finland.
authors.forename: Anniina
authors.initials: A
authors.lastname: Färkkilä
authors.affiliation: Pathology and HUSLAB, University of Helsinki and Helsinki University Hospital, Finland.
authors.forename: Ralf
authors.initials: R
authors.lastname: Bützow
authors.affiliation: Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Finland.
authors.forename: Arto
authors.initials: A
authors.lastname: Leminen
authors.affiliation: Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Tapper
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Finland; Department of Pediatrics, Washington University School of Medicine, St Louis Children's Hospital, St Louis, MO, United States.
authors.forename: Markku
authors.initials: M
authors.lastname: Heikinheimo
authors.affiliation: Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Finland.
authors.forename: Leila
authors.initials: L
authors.lastname: Unkila-Kallio
authors.affiliation: Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Finland.
authors.forename: Annika
authors.initials: A
authors.lastname: Riska
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005387:Finland / Q000453:epidemiology; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics; D006106:Granulosa Cell Tumor / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D013509:Gynecologic Surgical Procedures / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008197:Lymph Node Excision; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D009367:Neoplasm Staging; D017697:Premenopause; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D012421:Rupture / Q000209:etiology; D012422:Rupture, Spontaneous / Q000453:epidemiology*; D047368:Tumor Burden
chemical_list: C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors
keywords: Granulosa cell tumor; Prognosis; Recurrence