Clinico-pathological significance of TCGA classification and SWI/SNF proteins expression in undifferentiated/dedifferentiated endometrial carcinoma: A possible prognostic risk stratification

Background. Undifferentiated/dedifferentiated endometrial carcinoma (UEC/DDEC) is a heterogeneous entity, which may show any of the TCGA molecular signatures and loss of the switch/sucrose nonfermentable (SWI/SNF) proteins expression. Aim. To assess the clinico-pathological significance of the TCGA molecular groups and SWI/SNF proteins expression in UEC/DDEC, through a quantitative systematic review. Methods. Electronic databases were searched for all studies assessing the TCGA molecular groups, i.e. POLE mutant, mismatch repair-deficient (MMRd), p53-abnormal (p53abn) and no specific molecular profile (NSMP), and/or the SWI/SNF proteins (SMARCA4/BRG1, SMARCB1/INI1, ARID1B) expression in UEC/DDEC. Student t -test, Fisher's exact test and Kaplan-Meier survival analysis with long-rank test were used to assess differences among groups; a p-value<0.05 was considered significant. Results. Eight studies were included in the systematic review. Among the TCGA groups, the mean patient age was significantly higher in the p53abn group than in the NSMP group (p = 0.048). The POLE-mutant group showed advanced FIGO stage (III-IV) significantly less commonly than the NSMP (p = 0.003) and MMRd (p = 0.008) groups, and a significantly better prognosis than the NSMP (p = 0.007), MMRd (p = 0.011) and p53abn (p = 0.045) groups.The SWI/SNF-deficient cases showed a significantly worse prognosis than the SWI/ SNF-intact cases (p = 0.010), while no significant differences were found regarding patient age and FIGO stage. Conclusions. Among UEC/DDEC, POLE-mutant cases show good prognosis, while SWI/SNF-deficient cases show poor prognosis. The other TCGA molecular subtypes seem to be characterized by an intermediate biological behaviour. On this account, UEC/DDEC patients might be subdivided into three risk groups based on POLE and SWI/SNF status. Further studies are necessary in this field. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

This study evaluated the clinico-pathological significance of TCGA molecular groups and SWI/SNF protein expression in undifferentiated/dedifferentiated endometrial carcinoma (UEC/DDEC). The findings suggest that POLE-mutant cases exhibit a good prognosis, while SWI/SNF-deficient cases have a poor prognosis. Other TCGA molecular subtypes appear to have an intermediate biological behavior.