CONTEXT: Granulosa cell tumors (GCTs) are ovarian malignancies that produce estrogens, inhibins, and anti-Müllerian hormone (AMH). The molecular pathogenesis of GCTs is likely to involve defects in the genes regulating normal granulosa cell proliferation during folliculogenesis. OBJECTIVE: The objective of this study was to test the role of factors regulating the normal granulosa cell function, i.e. AMH, inhibin-alpha, SF-1 (steroidogenic factor-1), and GATA transcription factors in the pathobiology and clinical behavior of GCTs. DESIGN: We selected randomly a cohort of 80 GCT patients treated at our university hospital during 1971-2003, analyzed protein expression in the tumor samples embedded on a tissue microarray by immunohistochemistry, and correlated the data to clinical and histopathological parameters. RESULTS: We found no significant differences in the immunoreactivity levels of inhibin-alpha, GATA-6, FOG-2 (friend of GATA-2), or SF-1 in GCTs compared with normal granulosa cells. AMH expression was, however, low (i.e. reduced) in 69% of GCTs and correlated inversely with tumor size (P = 0.0025). In contrast, GATA-4 expression was high (i.e. resembled normal granulosa cells) in 44% of GCTs and correlated positively with clinical stage and recurrence (P = 0.0232 and P = 0.0038, respectively). Fifty of the 80 patients had a follow-up for at least 10 yr, and 13 of them had recurrence(s). In multivariate analysis of recurrence, the high GATA-4 expression remained the only independent factor (risk ratio, 9.2; 95% confidence interval, 2.0-43.3; P = 0.0048). CONCLUSIONS: The more aggressive GCTs retain a high GATA-4 expression, whereas the larger tumors lose the proliferation-suppressing AMH expression. The high GATA-4 expression in GCTs may serve as a marker of poor prognosis.
CONTEXT: Granulosa cell tumors (GCTs) are ovarian malignancies that produce estrogens, inhibins, and anti-Müllerian hormone (AMH). The molecular pathogenesis of GCTs is likely to involve defects in the genes regulating normal granulosa cell proliferation during folliculogenesis. OBJECTIVE: The objective of this study was to test the role of factors regulating the normal granulosa cell function, i.e. AMH, inhibin-alpha, SF-1 (steroidogenic factor-1), and GATA transcription factors in the pathobiology and clinical behavior of GCTs. DESIGN: We selected randomly a cohort of 80 GCT patients treated at our university hospital during 1971-2003, analyzed protein expression in the tumor samples embedded on a tissue microarray by immunohistochemistry, and correlated the data to clinical and histopathological parameters. RESULTS: We found no significant differences in the immunoreactivity levels of inhibin-alpha, GATA-6, FOG-2 (friend of GATA-2), or SF-1 in GCTs compared with normal granulosa cells. AMH expression was, however, low (i.e. reduced) in 69% of GCTs and correlated inversely with tumor size (P = 0.0025). In contrast, GATA-4 expression was high (i.e. resembled normal granulosa cells) in 44% of GCTs and correlated positively with clinical stage and recurrence (P = 0.0232 and P = 0.0038, respectively). Fifty of the 80 patients had a follow-up for at least 10 yr, and 13 of them had recurrence(s). In multivariate analysis of recurrence, the high GATA-4 expression remained the only independent factor (risk ratio, 9.2; 95% confidence interval, 2.0-43.3; P = 0.0048). CONCLUSIONS: The more aggressive GCTs retain a high GATA-4 expression, whereas the larger tumors lose the proliferation-suppressing AMH expression. The high GATA-4 expression in GCTs may serve as a marker of poor prognosis.
Authors: Riika Vähätalo; Tiina M Asikainen; Riitta Karikoski; Vuokko L Kinnula; Carl W White; Sture Andersson; Markku Heikinheimo; Marjukka Myllärniemi Journal: Neonatology Date: 2010-11-12 Impact factor: 4.035
Authors: Zhilin Liu; Yi A Ren; Stephanie A Pangas; Jaye Adams; Wei Zhou; Diego H Castrillon; Dagmar Wilhelm; JoAnne S Richards Journal: Mol Endocrinol Date: 2015-06-10
Authors: So-Youn Kim; Katherine Ebbert; Marilia H Cordeiro; Megan M Romero; Kelly A Whelan; Adrian A Suarez; Teresa K Woodruff; Takeshi Kurita Journal: Cancer Res Date: 2016-05-09 Impact factor: 12.701