Molecular Analysis of Mixed XXXX Shows Clonality in Most Cases.

@entity1204 @entity1131 @entity4348 @entity5
Mixed @entity1204 refers to a @entity5 that comprises 2 or more distinct histotypes. We studied 18 mixed-type @entity1204 -11 mixed serous and low-grade @entity4348 (SC/EC), 5 mixed clear cell and low-grade ECs (CCC/EC), and 2 mixed CCC and SCs (CCC/SC), using targeted next-generation sequencing and immunohistochemistry to compare the molecular profiles of the different histotypes present in each case. In 16 of 18 cases there was molecular evidence that both components shared a clonal origin. Eight cases (6 EC/SC, 1 EC/CCC, and 1 SC/CCC) showed an SC molecular profile that was the same in both components. Five cases (3 CCC/EC and 2 SC/EC) showed a shared endometrioid molecular profile and identical mismatch-repair @entity1131 in both components. A single SC/EC case harbored the same POLE exonuclease domain mutation in both components. One SC/CCC and 1 EC/CCC case showed both shared and unique molecular features in the 2 histotype components, suggesting early molecular divergence from a common clonal origin. In 2 cases, there were no shared molecular features, and these appear to be biologically unrelated @entity5 . Overall, these results show that the different histologic components in mixed @entity1204 typically share the same molecular aberrations. Mixed @entity1204 most commonly occur through morphologic mimicry, whereby @entity5 with serous-type molecular profile show morphologic features of EC or CCC, or through underlying deficiency in DNA nucleotide repair, with resulting rapid accrual of mutations and intratumoral phenotypic heterogeneity. Less commonly, mixed @entity1204 are the result of early molecular divergence from a common progenitor clone or are synchronous biologically unrelated @entity5 ( @entity5 ).
