EWSR1/FUS-CREB fusions define a distinctive malignant epithelioid neoplasm with predilection for mesothelial-lined cavities
| Autor: | Pedram Argani, Cristina R. Antonescu, Lei Zhang, Brendan C. Dickson, Yun Shao Sung, Albrecht Stenzinger, Isabel Harvey, G. Petur Nielsen, Albert J. H. Suurmeijer, Lysandra Voltaggio, Gunhild Mechtersheimer, Angela Takano |
|---|---|
| Přispěvatelé: | Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine fusion Pathology medicine.medical_specialty sarcoma Adolescent Oncogene Proteins Fusion translocation Soft Tissue Neoplasms Biology Article Pathology and Forensic Medicine Fusion gene CREM Young Adult 03 medical and health sciences Cytokeratin Peritoneal cavity 0302 clinical medicine Immunophenotyping ATF1 Biomarkers Tumor medicine Humans Neoplasm Mesothelioma Child Cyclic AMP Response Element-Binding Protein Angiomatoid fibrous histiocytoma Middle Aged medicine.disease 030104 developmental biology medicine.anatomical_structure EWSR1 030220 oncology & carcinogenesis CREB1 RNA-Binding Protein FUS Female RNA-Binding Protein EWS |
| Zdroj: | Modern Pathology, 2233-2243. Nature Publishing Group ISSUE=11;STARTPAGE=2233;ENDPAGE=2243;ISSN=0893-3952;TITLE=Modern Pathology Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc |
| ISSN: | 0893-3952 |
| Popis: | Gene fusions constitute pivotal driver mutations often encoding aberrant chimeric transcription factors. However, an increasing number of gene fusion events have been shown not to be histotype specific and shared among different tumor types, otherwise completely unrelated clinically or phenotypically. One such remarkable example of chromosomal translocation promiscuity is represented by fusions between EWSR1 or FUS with genes encoding for CREB-transcription factors family (ATF1, CREB1, and CREM), driving the pathogenesis of various tumor types spanning mesenchymal, neuroectodermal, and epithelial lineages. In this study, we investigate a group of 13 previously unclassified malignant epithelioid neoplasms, frequently showing an epithelial immunophenotype and marked predilection for the peritoneal cavity, defined by EWSR1/FUS-CREB fusions. There were seven females and six males, with a mean age of 36 (range 9-63). All except three cases occurred intra-abdominally, including one each involving the pleural cavity, upper, and lower limb soft tissue. All tumors showed a predominantly epithelioid morphology associated with cystic or microcystic changes and variable lymphoid cuffing either intermixed or at the periphery. All except one case expressed EMA and/or CK, five were positive for WT1, while being negative for melanocytic and other mesothelioma markers. Nine cases were confirmed by various RNA-sequencing platforms, while in the remaining four cases the gene rearrangements were detected by FISH. Eleven cases showed the presence of CREM-related fusions (EWSR1-CREM, 7; FUS-CREM, 4), while the remaining two harbored EWSR1-ATF1 fusion. Clinically, seven patients presented with and/or developed metastases, confirming a malignant biologic potential. Our findings expand the spectrum of tumors associated with CREB-related fusions, defining a novel malignant epithelioid neoplasm with an immunophenotype suggesting epithelial differentiation. This entity appears to display hybrid features between angiomatoid fibrous histiocytoma (cystic growth and lymphoid cuffing) and mesothelioma (peritoneal/pleural involvement, epithelioid phenotype, and cytokeratin and WT1 co-expression). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink