title: Prognostic significance of FOXL2 mutation and mRNA expression in adult and juvenile granulosa cell tumors of the ovary.
abstract: Recently, mutation of the FOXL2 gene has been consistently identified in adult granulosa cell tumors of the ovary. The purpose of this study is to investigate whether the FOXL2 mutation and mRNA expression have a role in the pathogenesis of juvenile and adult granulosa cell tumors and influence tumor progression. Thirty-four adult granulosa cell tumors and 20 juvenile granulosa cell tumors were examined for the presence of the FOXL2 (C402G) mutation. Expression levels were studied by quantitative PCR and immunohistochemistry. We found that FOXL2 (C402G) mutation was present in 19/27 (70%) of the adult type tumors but in none of the juvenile granulosa cell tumors (0/18). No correlation was encountered between the presence of FOXL2 mutation and various clinicopathologic parameters except for the presence of a different sex-cord component, which was more frequently found in the subgroup of wild-type adult granulosa cell tumors than in the mutated tumors. Patients with tumors harboring the FOXL2 (C402G) mutation had a worse disease-free survival than those with the wild-type gene. Expression levels of FOXL2 mRNA had an impact on disease-free survival in both adult and juvenile granulosa cell tumors. We also found that the mutated tumors had a higher immunohistochemical expression of the FOXL2 protein, and there was a linear correlation between mRNA and immunohistochemical FOXL2 expression in both adult and juvenile granulosa cell tumors. Patients with juvenile granulosa cell tumors and higher FOXL2 protein expression had worse overall survival and disease-free survival than those with negative or weakly immunoreactive tumors. Our data suggest that FOXL2 mutation and mRNA expression are of prognostic importance in both adult and juvenile granulosa cell tumors.
authors.affiliation: Department of Pathology, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Emanuela
authors.initials: E
authors.lastname: D'Angelo
authors.forename: Ana
authors.initials: A
authors.lastname: Mozos
authors.forename: Daiei
authors.initials: D
authors.lastname: Nakayama
authors.forename: Iñigo
authors.initials: I
authors.lastname: Espinosa
authors.forename: Lluis
authors.initials: L
authors.lastname: Catasus
authors.forename: Josefina
authors.initials: J
authors.lastname: Muñoz
authors.forename: Jaime
authors.initials: J
authors.lastname: Prat
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000235:genetics*; D006106:Granulosa Cell Tumor / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis*; D015996:Survival Rate; D013997:Time Factors; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger