Tutkimustuotos: OpinnäyteVäitöskirja


Adult-type granulosa cell tumors (AGCTs) belong to the sex cord-stromal group of ovarian tumors and account for 3-5% of ovarian neoplasms. Etiological factors of AGCTs remain mostly unknown, although studies have found a somatic missense mutation in the transcription factor FOXL2. AGCTs are usually diagnosed at an early stage and have a favorable prognosis compared with the more common epithelial ovarian cancer. However, tumor recurrence develops in up to 35% of patients, even in early-stage disease - often unpredictably and several years or even decades after the primary diagnosis. The aims of this study were to determine the incidence and epidemiological background of AGCTs in a large, multinational Nordic cohort and to estimate the incidence of other, especially endocrine-related primary malignancies among patients with AGCT. Furthermore, the objective was to describe the clinical characteristics and prognostic factors linked to AGCT–related recurrence and survival, and to introduce an optimal follow-up strategy for these patients. Our epidemiological registry study on AGCT incidence utilized the Finnish, Icelandic, Norwegian, and Swedish Cancer Registry data on AGCTs over several decades. We showed that the age-adjusted incidence rates were quite constant in 1953-2012: about 0.6-0.8 per 100,000 for most of the study period. The age-specific incidence was highest at 50-64 years of age, and there were no occupations with significantly increased risk of AGCT. The conclusions drawn from these results point to AGCT as a primarily sporadic, not exposure-related cancer, typically occurring in peri- or postmenopause. We estimated the incidence of other primary malignancies among AGCT patients using data from the Finnish Cancer Registry in 1968-2013. After AGCT, we found increased risks for cancers of the soft tissue and thyroid as well as leukemia, which likely indicate shared risk factors and therapy-induced side effects. The incidence of AGCT was significantly increased among women with previous breast cancer, suggesting shared hormonal etiology or treatment-induced effects. To evaluate the clinical and prognostic factors, all AGCT patients diagnosed at Helsinki University Hospital during nearly six decades were included in the clinical study cohort (n=240). After a histological review, we analyzed the clinical data for association with both AGCT-related and overall survival and tumor relapse. Of the original study cohort, the diagnosis was histologically confirmed in 78% of patients and molecularly confirmed for the FOXL2 mutation in 68% of patients. In multivariate analysis, stage was the only independent prognostic factor related to AGCT-specific survival. Spontaneous or iatrogenic tumor rupture was independently associated with tumor recurrence. By utilizing the extensive cancer registry data together with the internationally unique, large and carefully validated single-institute patient cohort, these studies reveal the diagnostic challenges of AGCTs, and provide novel epidemiological data and evidence-based tools to develop follow-up strategies for this rare cancer.
Myöntävä instituutio
  • Helsingin yliopisto
  • Unkila-Kallio, Leila, Valvoja
  • Riska, Annika, Valvoja
Myöntöpäivämäärä15 joulukuuta 2017
Painoksen ISBN978-951-51-3627-5
Sähköinen ISBN978-951-51-3628-2
TilaJulkaistu - 15 joulukuuta 2017
OKM-julkaisutyyppiG5 Tohtorinväitöskirja (artikkeli)


Yhteenveto-osa 79 s. ja 4 eripainosta


  • 3123 Naisten- ja lastentaudit

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