Nuclear Localization of SMAD3 as an Independent Predictor of Recurrence in Ovarian Adult Granulosa Cell Tumor

Background & Objective: Adult granulosa cell tumors (AGCTs) are potentially malignant ovarian neoplasms with a well-known tendency for local spread and recurrence, years after prolonged follow-up. This study investigated the immunohist-ochemical (IHC) expression of SMAD3 (mothers against decapentaplegic homolog 3) in AGCTs to evaluate its association with a number of confirmed AGCT prognostic variables. Materials & Methods: Upon database search, the clinicopathological data, slides, and paraffin blocks of 35 AGCTs were retrospectively retrieved from archives, then examined histopathologically, staged, and stained immunohistochemically using anti-SMAD3. After H scoring of "SMAD3", the clinicopathological associations were investigated in positive- and negative-SMAD3 expression groups using appropriate statistical methods. Regression analysis was performed to define independent predictors of recurrence in AGCT. Results: SMAD3 was actively expressed in the nuclei of 51.4% of AGCTs. It was significantly associated with tumor recurrence, capsular rupture, and size (P=0.011, 0.018, and 0.028, respectively), but not with age, presentation, laterality, stage, tumor morphological pattern, or mitotic index. Capsular rupture and tumor size were defined as highly significant (P≤0.001), as well as SMAD3+ve expression and FIGO stage as significant independent predictors of recurrence (P=0.05 and 0.049, respectively) in AGCT. Conclusion: SMAD3 is actively expressed in the tumor cell nuclei of around one half of AGCTs and this expression associates with high propensity for tumor recurrence, capsular rupture, and increasing tumor size. Along with the other observed independent predictors of recurrence, SMAD3 may provide an outline to direct discovery of new risk-stratification criteria as well as therapeutic targets for AGCTs.