1. SWI/SNF-deficiency defines highly aggressive undifferentiated endometrial carcinoma.
- Author
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Tessier-Cloutier B, Coatham M, Carey M, Nelson GS, Hamilton S, Lum A, Soslow RA, Stewart CJ, Postovit LM, Köbel M, and Lee CH
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma metabolism, Carcinoma pathology, DNA Helicases genetics, DNA Helicases metabolism, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Endometrial Neoplasms metabolism, Endometrial Neoplasms pathology, Female, Humans, Immunohistochemistry, Middle Aged, Nuclear Proteins genetics, Nuclear Proteins metabolism, Retrospective Studies, SMARCB1 Protein genetics, SMARCB1 Protein metabolism, Transcription Factors genetics, Transcription Factors metabolism, Carcinoma genetics, Endometrial Neoplasms genetics
- Abstract
Dedifferentiated/undifferentiated endometrial carcinoma (DDEC/UEC) is an endometrial cancer characterized by the presence of histologically undifferentiated carcinoma. Genomic inactivation of core switch/sucrose nonfermentable (SWI/SNF) complex proteins was recently identified in approximately two-thirds of DDEC/UEC. The aim of this study was to delineate the clinical behavior of SWI/SNF-deficient DDEC/UEC in comparison to SWI/SNF-intact DDEC/UEC. The study cohort consisted of 56 SWI/SNF-deficient DDEC/UEC (2 POLE-mutated), which showed either SMARCA4 (BRG1) loss, ARID1A/1B co-loss, or SMARCB1 (INI1) loss in the undifferentiated tumor, and 26 SWI/SNF-intact DDEC/UEC (4 POLE-mutated). The average age at diagnosis was 61 years for patients with SWI/SNF-deficient tumors and 64 years for SWI/SNF-intact tumors. Mismatch repair (MMR) protein deficiency was seen in 66% of SWI/SNF-deficient and 50% of SWI/SNF-intact tumors. At initial presentation, 55% of patients with SWI/SNF-deficient tumors had extrauterine disease spread in contrast to 38% of patients with SWI/SNF-intact tumors. The 2-year disease specific survival (DSS) for stages I and II disease was 65% for SWI/SNF deficient tumors relative to 100% for SWI/SNF-intact tumors (p = 0.042). For patients with stages III and IV disease, the median survival was 4 months for SWI/SNF-deficient tumors compared to 36 months for SWI/SNF-intact tumors (p = 0.0003). All six patients with POLE-mutated tumors, including one with stage IV SWI/SNF-deficient tumor were alive with no evidence of disease. Among the patients with advanced stage SWI/SNF-deficient tumors, 68% (21 of 31) received adjuvant or neoadjuvant chemotherapy (platinum/taxane-based) and all except the patient with a POLE-mutated tumor (20 of 21) experienced disease progression either during chemotherapy or within 4 months after its completion. These findings show that core SWI/SNF-deficiency defines a highly aggressive group of undifferentiated cancer characterized by rapid disease progression that is refractory to conventional platinum/taxane-based chemotherapy. This underscores the importance of accurate clinical recognition of this aggressive tumor and the need to consider alternative systemic therapy for these tumors., (© 2020 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.)
- Published
- 2021
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