Dedifferentiated/undifferentiated endometrial carcinoma:SWI/SNF-deficiency and molecular heterogeneity indicating novel prognostic stratification in a single-center study of 71 cases.

Deficiency of SWI/SNF proteins, particularly BRG1 (SMARCA4) and INI1 (SMARCB1), has frequently been associated with poor clinical outcomes in dedifferentiated/undifferentiated endometrial carcinoma (DDEC/UDEC). However, the prognostic significance of BRM (SMARCA2) remains unclear. Additionally, although the TCGA classification predicts outcomes in endometrioid adenocarcinoma, its prognostic value in DDEC/UDEC is still unproven. In this study, 71 DDEC/UDEC cases were assessed for the expression of BRG1, BRM, INI1 and ARID1A. BRG1, BRM, INI1 and ARID1A deficiency were observed in 36% (26/71), 55% (27/49), 8% (6/69), 55% (19/34) of cases, respectively. BRG1-deficiency, and BRG1 or INI1-deficiency were both associated with poorer overall survival (OS) (P = 0.048, P = 0.013, respectively). Only BRG1 or INI1-deficiency was significantly correlated with worse disease-free survival (DFS) (P = 0.039). No significant differences in either DFS or OS were observed between patients with isolated loss of BRM or INI1 expression and those with intact expression. Genetic alterations in 31 cases predominantly involved the PI3K-AKT-MTOR pathway. TCGA molecular subtyping showed no significant differences in OS (P = 0.488) or DFS (P = 0.425) among the molecular subtypes. However, patients with concurrent microsatellite instability-high (MSI-H) and PIK3CA mutation exhibited more favorable OS (P = 0.021) and DFS (P = 0.012). Therefore, our research shows that BRG1 or INI1 deficiency, especially BRG1 deficiency, predicts a poorer prognosis in patients with DDEC/UDEC. Furthermore, other integrated molecular classification strategies--such as the combination of MSI-H status and PIK3CA mutation--may provide a novel prognostic stratification approach for this aggressive tumor entity.