title: HER2 and GATA4 are new prognostic factors for early-stage ovarian granulosa cell tumor-a long-term follow-up study.
abstract: Granulosa cell tumors (GCTs) carry a risk of recurrence also at an early stage, but reliable prognostic factors are lacking. We assessed clinicopathological prognostic factors and the prognostic roles of the human epidermal growth factor receptors (HER 2-4) and the transcription factor GATA4 in GCTs. We conducted a long-term follow-up study of 80 GCT patients with a mean follow-up time of 16.8 years. A tumor-tissue microarray was immunohistochemically stained for HER2-4 and GATA4. Expression of HER2-4 mRNA was studied by means of real time polymerase chain reaction and HER2 gene amplification was analyzed by means of silver in situ hybridization. The results were correlated to clinical data on recurrences and survival. We found that GCTs have an indolent prognosis, with 5-year disease-specific survival (DSS) being 97.5%. Tumor recurrence was detected in 24% of the patients at a median of 7.0 years (range 2.6-18 years) after diagnosis. Tumor stage was not prognostic of disease-free survival (DFS). Of the molecular prognostic factors, high-level expression of HER2, and GATA4, and high nuclear atypia were prognostic of shorter DFS. In multivariate analyses, high-level coexpression of HER2 and GATA4 independently predicted DFS (hazard ratio [HR] 8.75, 95% CI 2.20-39.48, P = 0.002). High-level expression of GATA4 also predicted shorter DSS (HR 3.96, 95% CI 1.45-12.57, P = 0.006). In multivariate analyses, however, tumor stage (II-III) and nuclear atypia were independent prognostic factors of DSS. In conclusion HER2 and GATA4 are new molecular prognostic markers of GCT recurrence, which could be utilized to optimize the management and follow-up of patients with early-stage GCTs.
authors.affiliation: Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Anniina
authors.initials: A
authors.lastname: Färkkilä
authors.forename: Noora
authors.initials: N
authors.lastname: Andersson
authors.forename: Ralf
authors.initials: R
authors.lastname: Bützow
authors.forename: Arto
authors.initials: A
authors.lastname: Leminen
authors.forename: Markku
authors.initials: M
authors.lastname: Heikinheimo
authors.forename: Mikko
authors.initials: M
authors.lastname: Anttonen
authors.forename: Leila
authors.initials: L
authors.lastname: Unkila-Kallio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D050991:GATA4 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006106:Granulosa Cell Tumor / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D050991:GATA4 Transcription Factor; D018719:Erb-b2 Receptor Tyrosine Kinases; C484170:GATA4 protein, human; C508053:ERBB2 protein, human
keywords: GATA4; HER2; granulosa cell tumor; prognostic factor; recurrence; survival