Role of SMARCA4 (BRG1) and SMARCB1 (INI1) in Dedifferentiated Endometrial Carcinoma With Paradoxical Aberrant Expression of MMR in the Well-Differentiated Component: A Case Report and Review of the Literature

Abstract

Introduction Dedifferentiated endometrial carcinoma is an uncommon highly aggressive uterine tumor. It comprises 2 components: a well-differentiated, low-grade epithelial carcinoma and an undifferentiated carcinoma. The undifferentiated carcinoma frequently exhibits rhabdoid cytologic features. Many of these tumors are characterized by an aberrant switch/sucrose non-fermenting (SWI/SNF) complex. They may also exhibit aberrant expression of mismatch repair (MMR) proteins. Together, these play an important role in the pathogenesis and aggressive nature of the tumor. Material and Methods We present a case of dedifferentiated endometrial carcinoma in a 63-year-old female showing loss of expression of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4/BRG1), and aberrant expression of MMR proteins. We also review the literature starting from the earliest recognition of this entity and the various studies done to explain its molecular pathogenesis and prognostic importance. Results and Conclusions Recognition of SWI/SNF complex-deficient dedifferentiated endometrial carcinoma is important as these tumors do not respond to platinum-based chemotherapy, and consideration of alternative therapies is often necessary. We also want to emphasize that though most of the studies have found MMR deficiency in the undifferentiated carcinoma component, it may be seen only in the low-grade, well-differentiated component, as observed in this case.

Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next generation sequencing data analysis

“…VCAM1 [1413], PTPRD (protein tyrosine phosphatase receptor type D) [1426] and hsa-mir-17-5p [1689] are associated with prognosis in patients with gestational diabetes mellitus. IGF2BP1 [453], DAPK1 [183], PTPRD (protein tyrosine phosphatase receptor type D) [412], TCF3 [1690], SMARCA4 [1691] and TRIM28 [1692] biomarkers are vital for endometrial cancer. Research have shown that PTPRD (protein tyrosine phosphatase receptor type D) [656], PDGFB (platelet derived growth factor subunit B) [642], DAPK1 [751], hsa-mir-4432 [1693], SMARCA4 [1694] and TRIM28 [1695] participates in hypertension.…”

STK11 loss and SMARCB1 deficiency mutation in a dedifferentiated lung cancer patient present response to neo-adjuvant treatment with pembrolizumab and platinum doublet: A case report

“…Mutation of SMARCB1 was frequently presented in sinonasal carcinoma, gastrointestinal cancer, and pancreatic cancer types, however, rarely reported in lung carcinoma (13,14). According to the former literature, cancer patients with pathologic SMARCB1 mutations were reported resulting in a worse prognosis independently from the conventional treatment strategies including chemotherapy, radiation therapy or surgery (12,15,16).…”

Rare Subtype of Endometrial Cancer: Undifferentiated/Dedifferentiated Endometrial Carcinoma, from Genetic Aspects to Clinical Practice

“…Generally, endometrioid carcinoma is a hormone-dependent tumor that expresses hormone receptors that may respond to hormone therapy. Unfortunately, UDEC seldom has detectable hormone receptors and its tumorigenesis pathway has distinct features, such as microsatellite instability (MSI-H)/mismatch repair (MMR) protein [ 8 , 9 ] and the genomic inactivation of core components of the SWI/SNF chromatin-remodeling complex [ 10 , 11 ].…”