Striking Association of Lymphoid Enhancing Factor (LEF1) Overexpression and DUSP22 Rearrangements in Anaplastic Large Cell Lymphoma.
Biomarkers, Tumor
/ analysis
Databases, Factual
Dual-Specificity Phosphatases
/ genetics
Gene Expression Regulation, Neoplastic
Gene Rearrangement
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Lymphoid Enhancer-Binding Factor 1
/ analysis
Lymphoma, Large-Cell, Anaplastic
/ enzymology
Mitogen-Activated Protein Kinase Phosphatases
/ genetics
Up-Regulation
Wnt Signaling Pathway
Journal
The American journal of surgical pathology
ISSN: 1532-0979
Titre abrégé: Am J Surg Pathol
Pays: United States
ID NLM: 7707904
Informations de publication
Date de publication:
01 04 2021
01 04 2021
Historique:
pubmed:
10
11
2020
medline:
11
5
2021
entrez:
9
11
2020
Statut:
ppublish
Résumé
Anaplastic large cell lymphomas (ALCLs) are broadly classified into ALK-positive and ALK-negative. ALK-negative ALCL is composed of DUSP22-rearranged, TP63-rearranged, and triple-negative cases. While lymphoid enhancer-binding factor (LEF1) plays a crucial role in T-cell maturation, limited data exist on its expression in T-cell lymphomas, including ALCL. We characterized the expression of LEF1 in ALCL by immunohistochemistry. LEF1 nuclear expression in the neoplastic cells was graded as negative (0), weak (1+), intermediate (2+), or strong (3+), with the percentage of LEF1-positive neoplastic cells recorded. A total of 45 ALCL cases were evaluated, of which 16 were DUSP22-rearranged. About 93.8% (15/16) DUSP22-rearranged cases showed strong expression of LEF1 in >75% tumor cells, compared with 3.4% (1/29) non-DUSP22-rearranged ALCL (P<0.0001). The striking association of LEF1 protein overexpression with DUPS22 rearrangement in ALCL was further confirmed by a gene expression profiling study which revealed significantly higher LEF1 expression in DUSP22-rearranged ALCL compared with other ALCL subtypes (P=0.0001). Although LEF1 is a nuclear mediator of the Wnt/β-catenin pathway, CTNNB1 RNA and protein levels were not overexpressed in LEF1-positive cases, suggesting the LEF1 overexpression in ALCL may not be involved in the Wnt/β-catenin pathway. The strong and uniform LEF1 expression pattern has a high positive predictive value (93.8%) and high negative predictive value (96%) for DUSP22 rearrangement in ALK-negative ALCL. The combination of characteristic morphologic and molecular features of DUSP22-rearranged cases with the high LEF1 expression further emphasizes that DUSP22-rearranged ALCL represents a distinct clinicopathologic subset of ALCL.
Identifiants
pubmed: 33165091
pii: 00000478-202104000-00013
doi: 10.1097/PAS.0000000000001614
doi:
Substances chimiques
Biomarkers, Tumor
0
LEF1 protein, human
0
Lymphoid Enhancer-Binding Factor 1
0
Mitogen-Activated Protein Kinase Phosphatases
EC 3.1.3.16
DUSP22 protein, human
EC 3.1.3.48
Dual-Specificity Phosphatases
EC 3.1.3.48
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
550-557Informations de copyright
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
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