Nuclear Localization of SMAD۳ 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 immunohistochemical (IHC) expression of SMAD۳ (mothers against decapentaplegic homolog ۳) in AGCTs to evaluate its association with a number of confirmed AGCT prognostic variables. Prognostic predictors of recurrence in AGCT were further defined. Methods: Upon database search, the clinicopathological data, slides, and paraffin blocks of ۳۵ AGCTs were retrospectively retrieved from archives, then examined histopathologically, staged, and stained immunohistochemically using anti-SMAD۳. After H scoring of SMAD۳, the clinicopathological associations were investigated in positive- and negative-SMAD۳ expression groups using appropriate statistical methods. Regression analysis was performed to define independent predictors of recurrence in AGCT. Results: SMAD۳ was actively expressed in the nuclei of ۵۱.۴% of AGCTs. It was significantly associated with tumor recurrence, capsular rupture, and size (P=۰.۰۱۱, ۰.۰۱۸, and ۰.۰۲۸, 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≤۰.۰۰۱), as well as SMAD۳+ve expression and FIGO stage as significant independent predictors of recurrence (P=۰.۰۵ and ۰.۰۴۹, respectively) in AGCT. Conclusion: SMAD۳ 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, SMAD۳ may provide an outline for direct discovery of new risk-stratification criteria as well as therapeutic targets for AGCTs.

کلیدواژه ها:

AGCT ، Immunohistochemistry ، Independent predictors ، Recurrence ، SMAD۳