NFATc2-rearranged sarcomas: clinicopathologic, molecular, and cytogenetic study of 7 cases with evidence of AGGRECAN as a novel diagnostic marker

NFATc2 -rearranged sarcomas ( NFATc2 -Sarcomas) are infrequent round cell tumors characterized by EWSR1-NFATc2 fusions and FUS-NFATc2 fusions. Although our knowledge on these neoplasms has increased recently, novel diagnostic tools and more comprehensive series are still needed. Here, we describe th...

Full description

Saved in:
Bibliographic Details
Published in:Modern pathology Vol. 33; no. 10; pp. 1930 - 1944
Main Authors: Perret, Raul, Escuriol, Julien, Velasco, Valérie, Mayeur, Laetitia, Soubeyran, Isabelle, Delfour, Christophe, Aubert, Sébastien, Polivka, Marc, Karanian, Marie, Meurgey, Alexandra, Le Guellec, Sophie, Weingertner, Noelle, Hoeller, Sylvia, Coindre, Jean-Michel, Larousserie, Frédérique, Pierron, Gaëlle, Tirode, Franck, Le Loarer, François
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01.10.2020
Elsevier Limited
Nature Publishing Group: Open Access Hybrid Model Option B
Subjects:
13/51
14/32
14/63
38/39
38/43
38/91
692/699/67/1344
692/699/67/1798
Adult
Aged
Aggrecan
Aggrecans - metabolism
Biomarkers, Tumor - metabolism
Bone cancer
Bone Neoplasms - diagnosis
Bone Neoplasms - genetics
Bone Neoplasms - metabolism
Bone tumors
Cancer
CD99 antigen
Chemotherapy
Chondrosarcoma
Cytogenetics
Desmin
Female
Femur
FLI-1 protein
Humans
Ilium
Immunohistochemistry
Karyotypes
Keratin
Laboratory Medicine
Life Sciences
Male
Medical diagnosis
Medicine
Medicine & Public Health
Mesenchyme
Middle Aged
Neoplasia
NFATC Transcription Factors - genetics
Oncogene Fusion
Oncogene Proteins, Fusion - genetics
Osteoid
Pathology
Patients
Pleomorphism
Sarcoma
Sarcoma - diagnosis
Sarcoma - genetics
Sarcoma - metabolism
Soft tissues
Stroma
Surgery
Tibia
Tumor suppressor genes
Tumors
ISSN:0893-3952, 1530-0285, 1530-0285
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:NFATc2 -rearranged sarcomas ( NFATc2 -Sarcomas) are infrequent round cell tumors characterized by EWSR1-NFATc2 fusions and FUS-NFATc2 fusions. Although our knowledge on these neoplasms has increased recently, novel diagnostic tools and more comprehensive series are still needed. Here, we describe the features of a series of seven molecularly confirmed NFATc2 -Sarcomas ( EWSR1 - NFATc2 , n  = 4; FUS - NFATc2 , n  = 3) and demonstrate the utility of AGGRECAN immunohistochemistry for their identification. Patients were four males and three females, ranging in age from 19 to 66 years (median: 33). All were primary bone tumors (femur, n  = 4; tibia, n  = 2; ilium, n  = 1), frequently infiltrating the surrounding soft tissues. Treatment often consisted of neoadjuvant chemotherapy and surgery. Follow-up was available for six patients (median 18 months, range 5–102 months), three patients died of disease and four patients are currently alive. Histologically, tumors consisted of monotonous round cells growing in lobules and sheets in variable amounts of fibrous to myxoid stroma. Other findings included spindle cells, corded and trabecular architecture, nuclear pleomorphism, cartilaginous differentiation, and osteoid-like matrix. Histological response to neoadjuvant chemotherapy was poor in all resection specimens available for review ( n  = 4). Tumors were diffusely positive for AGGRECAN and CD99 (7/7), and a subset expressed Pan-Keratin (AE1-AE3; 3/6), S100 (2/6), BCOR (2/6), ETV-4 (2/5), WT1 (2/6), and ERG (2/5). Desmin, NKX3-1, and SATB2 were negative (0/6). Diffuse AGGRECAN staining was also seen in 8/129 round cell sarcomas used for comparison, including mesenchymal chondrosarcoma (7/26) and CIC -sarcoma (1/26). Array-CGH showed complex karyotypes with recurrent deletions of tumor suppressor genes ( CDKN2A/B, TUSC7, and DMD) in three FUS-NFATC2 cases and a simpler profile without homozygous losses in one EWSR1 - NFATc2 case. Segmental chromosomal gains covering the loci of the fusion genes were detected in both variants. Overall, our study confirms and expands previous observations on NFATc2 -sarcomas and supports that AGGRECAN is a useful biomarker of these tumors.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:0893-3952
1530-0285
1530-0285
DOI:10.1038/s41379-020-0542-z