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

New Pathological and Clinical Insights in Endometrial Cancer in View of the Updated ESGO/ESTRO/ESP Guidelines

“…The MMRd group is the most represented (about half of cases) [ 53 ]. Consistently with what observed in the other histotypes, POLEmut UEC/DEC have shown excellent prognosis, deserving the inclusion in the low-grade risk category of the ESGO/ESTRO/ESP system [ 18 , 52 ]. Significant prognostic differences could not be found among the three other groups, which showed poor prognosis.…”

“…Indeed, the favorable prognostic value of the POLEmut group appears not to significantly change when normalized for possible confounding factors [ 13 ]. The excellent prognosis of the POLEmut group is maintained across the several histotypes, justifying the guidance of the ESGO/ESTRO/ESP guidelines [ 12 , 23 , 33 , 34 , 35 , 43 , 44 , 52 , 63 , 64 ]. On the other hand, the prognosis of the NSMP group appears heavily affected by tumor grade and histotype.…”

“…UEC/DEC might be confused with high-grade EEC, SEC with solid growth pattern, NEEC, carcinosarcoma, or sarcomas, and is probably underrecognized in the common practice [ 51 ]. Most UEC/DEC show a loss of SWI/SNF complex proteins expression, which seem to be associated with dedifferentiation [ 52 ]. Consistently regarded as an aggressive entity, UEC/DEC has shown molecular heterogeneity.…”

“…Significant prognostic differences could not be found among the three other groups, which showed poor prognosis. However, it has recently emerged that the loss of expression of certain SWI/SNF complex proteins expression, i.e., ARID1B, SMARCA4, and SMARCB1, is associated with very poor prognosis, even worse than that of carcinosarcomas [ 49 , 52 ]. We may hypothesize that these SWI/SNF-deficient UEC/DEC might deserve a still more aggressive management than non-endometroid carcinomas and be considered at high risk even in the absence of myometrial invasion, similarly to the recommendation of the NCCN (National Comprehensive Cancer Network) guidelines [ 54 ].…”

“…We might hypothesize that the high prevalence and poor prognosis of the MMRd group is due to the inclusion of highly aggressive UDC/DEC. In fact, DEC may mimic UCS, shows a MMRd signature in over 40% of cases, and may have very poor prognosis in the case of SWI/SNF-deficiency (as discussed above) [ 52 , 53 ]. On this account, we believe that an accurate prognostic evaluation of MMRd UCS should take place after careful exclusion of UEC/DEC cases and especially of SWI/SNF cases.…”