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.
Subject(s)
Biomarkers, Tumor/genetics , Forkhead Transcription Factors/genetics , Granulosa Cell Tumor/genetics , Mutation , Ovarian Neoplasms/genetics , RNA, Messenger/analysis , Adolescent , Adult , Age Factors , Aged , Biomarkers, Tumor/analysis , DNA Mutational Analysis , Disease-Free Survival , Female , Forkhead Box Protein L2 , Forkhead Transcription Factors/analysis , Granulosa Cell Tumor/chemistry , Granulosa Cell Tumor/mortality , Granulosa Cell Tumor/pathology , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Middle Aged , Ovarian Neoplasms/chemistry , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Polymerase Chain Reaction , Prognosis , Proportional Hazards Models , Survival Rate , Time Factors , Up-Regulation , Young AdultABSTRACT
OBJECTIVES: The aim of this study was to assess the prognostic factor of radical surgery in patients with stage IIIc ovarian cancer. STUDY DESIGN: Fifty-two patients were subjected to the study. The complete resection or optimal primary cytoreductive surgery (OPCS) was set as the maximum effort, and the accomplishment rate and prognosis were assessed. In addition, the poor prognosis cases among the OPCS-accomplished were evaluated with several factors based on univariate and multivariate analyses. RESULTS: The OPCS accomplishment rate was 84.6%. A worse prognosis was obtained in the more-than-4-weeks-delayed postoperative chemotherapy group, assessing poor-outcome cases in the OPCS group. A case that required more than three colon resections was the significant factor for the delay of postoperative chemotherapy. CONCLUSIONS: OPCS should be performed with maximum effort to improve the prognosis of stage IIIc ovarian cancer. We should avoid any delay in starting postoperative chemotherapy. In cases that require more than three colon resections, it seems that 'perioperative management' should be reconsidered and that priority should be given to postoperative management so that chemotherapy can be started soon after the operation.
