Loss of expression of SMARCA4 (BRG1), SMARCA2 (BRM) and SMARCB1 (INI1) in undifferentiated carcinoma of the endometrium is not uncommon and is not always associated with rhabdoid morphology.

Abstract

Abnormalities of SMARCB1 (INI1), which encodes a member of the SWI/SNF pathway, are found in neoplasms with rhabdoid morphology, such as malignant rhabdoid tumour of the kidney and atypical teratoid/rhabdoid tumour of the central nervous system. SMARCA4 (BRG1), which encodes another member of the SWI/SNF pathway, and which is mutated in almost all small-cell carcinomas of the ovary, hypercalcaemic type, has been investigated in endometrial carcinomas, and mutations with resultant loss of immunohistochemical staining have been demonstrated in some endometrial undifferentiated carcinomas/dedifferentiated carcinomas. The aim of this study was to evaluate immunohistochemical expression of SMARCA4, SMARCB1 and SMARCA2 in a cohort of undifferentiated endometrial carcinomas, and to correlate expression of these markers with rhabdoid morphology and clinical outcome. Forty undifferentiated endometrial carcinomas (18 pure and 22 dedifferentiated carcinomas) were stained with SMARCA4 (n = 40), SMARCB1 (n = 27), and SMARCA2 (n = 37). SMARCA4 expression was intact in 26 of 40 (65%) cases, lost in 13 of 40 (32.5%) cases, and unassessable in one case (2.5%). SMARCB1 expression was intact in 26 of 27 (96%) cases and lost in one of 27 (4%) cases. SMARCA2 expression was intact in 23 of 37 (62%) cases, lost in 10 of 37 (27%) cases, and unassessable in four cases. SMARCA2 expression showed corresponding loss in nine of the 13 (69%) SMARCA4-deficient cases. Rhabdoid morphology was present in three of 13 (23%) SMARCA4-deficient cases, in two of 10 (20%) SMARCA2-deficient cases, in four of 26 (15%) SMARCA4-intact cases, and in four of 23 (17%) SMARCA2-intact cases. There was no correlation between SMARCA4 or SMARCA2 expression and clinical outcome. Our study demonstrated that almost one-third of endometrial undifferentiated carcinomas show loss of SMARCA4 and SMARCA2 expression, and that a subset show rhabdoid morphology. The majority of the SMARCA4-deficient cases show concomitant loss of SMARCA2 expression. There is no correlation between SMARCA4 or SMARCA2 expression and outcome. Our results confirm that the SWI/SNF chromatin-remodelling complex is involved in the pathogenesis of endometrial undifferentiated carcinomas.