SWI/SNF complex deficiency and mismatch repair protein expression in undifferentiated and dedifferentiated endometrial carcinoma

Abstract

Undifferentiated endometrial carcinoma (UEC) is a relatively uncommon but clinically aggressive uterine malignancy. In common with a subset of poorly differentiated carcinomas arising in other sites, UEC may exhibit rhabdoid morphology and be associated with a low-grade tumour component (dedifferentiated carcinoma). Recent studies have implicated inactivation of the SWI/SNF complex subunits in the aforementioned extrauterine tumours. Therefore we have examined INI1 (SMARCB1), BRG1 (SMARCA4), and BAF250a (ARID1A) immunostaining, and also expression of the DNA mismatch repair (MMR) proteins MLH1, PMS2, MSH2 and MSH6 in 22 UEC, seventeen of which were dedifferentiated. Abnormal SWI/SNF subunit expression was detected in four dedifferentiated carcinomas including three with loss of BRG1 staining limited to the undifferentiated tumour component and one case with loss of INI1 expression in both low- and high-grade elements; the latter case also showed BAF250a deficiency in the undifferentiated tumour cells. Abnormal MMR protein expression was identified in 13 tumours (59%) including nine with concurrent loss of MLH1 and PMS2. These findings suggest that SWI/SNF subunit alterations may play a role in the progression/ dedifferentiation of endometrial carcinoma, and that SWI/SNF and MMR protein deficiencies may act synergistically in deregulating DNA repair mechanisms in these tumours.