DNA mismatch repair deficiency and p53 abnormality are age-related events in mixed endometrial carcinoma with a clear cell component

Mixed endometrial carcinoma (MEC) is defined as a tumor composed of two or more spatially distinct subtypes, at least one of which is serous or clear cell carcinoma. In this study, the clinicopathological features of 15 MEC cases containing a clear cell component (MEC-C) were investigated. The ages of patients ranged from 32 to 83 years (median, 61 years). The combinations of carcinoma components observed were endometrioid and clear cell in ten patients; endometrioid, clear cell and serous in three; and clear cell and serous in two. Immunohistochemically, nine had DNA mismatch repair (MMR) protein deficiency (MMR-d), nine had loss of ARID1A and three cases had aberrant p53 expression. MMR-d and loss of ARID1A showed a strong correlation. Only one case showed both MMR-d and aberrant p53 expression. The patients with MMR-d were younger than those without MMR-d (median; 58 years vs. 71 years). Loss of ARID1A also showed significant predilection for younger women than ARID1A intact cases. In conclusion, MMR-d was observed in 60 % of MEC-C, showed predilection for young women, and was associated with ARID1A loss. In contrast, non- MMR-d MEC-C occurred in elder women and some tumors may associate with TP53 mutation. These findings suggest that MEC-C develop via two different molecular mechanisms and they are age-related events.