SMARCA4-deficient uterine tumors in young women: response to immune checkpoint inhibitors

Int Cancer Conf J. 2024 Sep 17;13(4):515-519. doi: 10.1007/s13691-024-00721-2. eCollection 2024 Oct.

Abstract

SMARCA4-deficient tumors have been reported in various organs and are associated with a poor prognosis. SMARCA4-deficient undifferentiated uterine sarcoma (SDUS) was first described in 2018. Conversely, loss of SMARCA4 (BRG1) expression, as observed by immunostaining, has been observed in several cases of undifferentiated endometrial carcinoma. SDUS has considerable morphologic overlap with undifferentiated endometrial carcinoma, while there are differences in their clinicopathological features. Here, we present two cases of SMARCA4-deficient uterine tumors in patients in their 20 s: SDUS (Case 1) and undifferentiated endometrial carcinoma without SMARCA4 nuclear expression (Case 2). Using comprehensive genome profiling, we found that both cases had SMARCA4 mutations, with tumor mutation burdens of 0 and 68 Muts/Mb, respectively. Case 1 had multiple lung metastases 9 months after surgery. We treated the patients with combination of an immune checkpoint inhibitor (pembrolizumab) and a multikinase inhibitor (lenvatinib), and the response to the treatment was stable. This study presents the first report on the response to immune checkpoint inhibitor and multikinase inhibitor in SDUS.

Supplementary information: The online version contains supplementary material available at 10.1007/s13691-024-00721-2.

Keywords: ICIs; SDUS; SMARCA4; Undifferentiated endometrial carcinoma.