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ObjectiveTo evaluate the clinicopathologic characteristics and prognostic factors of ovarian granulosa cell tumors.MethodsMedical records of 113 patients presenting between January 1995 and December 2007 were retrospectively reviewed.ResultsOne-hundred two patients had adult type disease, with a mean age of 46.2 years (range, 18 to 83 years) and a mean follow-up period of 54.7 months (range, 1 to 155 months). The distribution of FIGO stages was 86 patients at stage I, 11 at stage II, and 5 at stage III. During follow-up, ten patients recurred at a mean time of 48 months (range, 4 to 109 months). Among them, three patients died after a mean of 57 months (range, 25 to 103 months). In recurrence analysis, advanced stage (p=0.032) and presence of residual disease (p=0.012) were statistically significant, and age<40 years, premenopause and positive washing cytology were marginally significant (p<0.1). In multivariate analysis, stage was the only factor associated with recurrence; adjuvant chemotherapy and fertility-sparing surgery were not statistically significant. Among 36 patients with fertility-sparing operations, eight patients had nine pregnancies and delivered seven babies. Eleven patients had juvenile type tumors; the mean age was 20.0 years (range, 8 to 45 years) and the mean follow-up period was 69.8 months (range, 20 to 156 months). The distribution of FIGO stage was nine patients at stage I and two at stage III. There were no recurrences or deaths reported. Four patients had seven pregnancies and delivered six babies.ConclusionStage is the only factor associated with disease-free survival, and fertility-sparing surgery may be a treatment option for women with early-stage disease who want to retain fertility.

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Results: Of the 68 patients, 43 had FIGO stage IB1 SCNEC, 15 had stage IB2, and 10 had stage IIA. Seven were treated with radical surgery alone; 11 with neoadjuvant chemotherapy (NACT) followed by radical surgery; 24 with radical surgery followed by adjuvant chemotherapy; and 26 with radical surgery followed by adjuvant radiation or chemoradiation. After a median follow-up of 44 months (range, 6-113 months), the 2-year and 5-year survival rates for all patients were 64.6% and 46.6%, respectively. Univariate and multivariate analysis showed that FIGO stage was predictive of poor prognosis. Patients who received NACT showed poorer prognosis than those who did not receive NACT. Adjuvant chemoradiation did not improve survival compared with adjuvant chemotherapy alone.Conclusions: FIGO stage may act as a surrogate for factors prognostic of survival. Primary radical surgery followed by adjuvant chemotherapy is the preferred treatment modality for patients with early stage SCNEC.

We provide detailed mechanisms of Ahnak-mediated potentiation of transforming growth factor β (TGFβ) signaling, which leads to a negative regulation of cell growth. We show that Smad3 interacts with Ahnak through MH2 domain and that Ahnak stimulates Smad3 localization into nucleus leading to potentiating TGFβ-induced transcriptional activity of R-Smad. Moreover, overexpression of Ahnak resulted in growth retardation and cell cycle arrest through downregulation of c-Myc and cyclin D1/D2. We describe results from analyses of Ahnak−/− mouse model expressing middle T antigen in a mammary gland-specific manner (MMTVTg/+Ahnak−/−), which showed significantly progressed hyperplasia of mammary glands compared with MMTVTg/+Ahnak+/+. Finally, we screened multiple human breast cancer tissues and showed that the expression of Ahnak in cancer tissues is lower than that in control tissues by 50%. Taken together, these data indicate that Ahnak mediates a negative regulation of cell growth and acts as novel tumor suppressor through potentiation of TGFβ signaling.

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Patupilone did not demonstrate significant improvement in OS compared with the active control, PLD. No new or unexpected serious AEs were identified.