Summary:
Granulosa cell tumors (GCTs) comprise 2% to 5% of ovarian neoplasms, with
unpredictable patterns of recurrence. The HER family, GATA4, and SMAD3 genes are
reportedly involved in GCT proliferation and apoptosis and may serve as new
predictors of recurrence. The aim of the study was to evaluate novel predictors
of recurrence in GCT from a large single institution cohort. Patients diagnosed
with GCTs (n = 125) between 1975 and 2014 were identified. Clinicopathologic
parameters were obtained and immunohistochemical evaluation was performed of
calretinin, inhibin, HER2, CD56, SMAD3, and GATA4. Statistical analyses were
conducted using Fisher exact test and Kaplan-Meier survival curves and Cox
regression analysis. The median follow-up period was 120 months (range,
1–465 mo). Recurrence was noted in 12/125 (9.6%) patients. Kaplan-Meier
analysis showed a shorter mean disease-free interval in whites versus blacks
(P = 0.001), stage III-IV versus stage I-II
(P = 0.0001), patients treated with surgery+chemotherapy
versus surgery (P = 0.0001), mitotic rate ≥4
(P = 0.005), severe nuclear pleomorphism
(P = 0.013), high HER2 expression (P =
0.001), high CD56 expression (P = 0.001), and high SMAD3
expression (P = 0.001). On Cox regression analysis, SMAD3 and
type of treatment received were the only 2 independent prognostic factors for
disease-free interval (P = 0.03 and P = 0.007,
respectively). On subanalysis for early-stage (stage I) GCTs, the need for
adjuvant chemotherapy and high expression of SMAD3 continued to be independent
predictors of recurrence (HR = 10.2, P = 0.01 and HR = 8.9,
P = 0.001, respectively).