The clinicopathologic significance of NPM1 mutation and ability to detect mutated NPM1 by immunohistochemistry in non-AML myeloid neoplasms.

Autor: Kaseb H; Department of Pathology, University of Central Florida College of Medicine, Orlando, Florida, USA., Visconte V; Department of Translational Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA., Socha DS; Department of Pathology, OhioHealth, Riverside Methodist Hospital, Columbus, Ohio, USA., Crane GM; Department of Laboratory Medicine, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA., Durkin L; Department of Laboratory Medicine, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA., Cook JR; Department of Laboratory Medicine, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA., Maciejewski JP; Department of Translational Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA., Hsi ED; Department of Pathology and Laboratory Medicine, Wake Forest School of Medicine, Wake Forest Baptist Health, Winston-Salem, North Carolina, USA., Rogers HJ; Department of Laboratory Medicine, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Jazyk: angličtina
Zdroj: Genes, chromosomes & cancer [Genes Chromosomes Cancer] 2023 Oct; Vol. 62 (10), pp. 573-580. Date of Electronic Publication: 2023 Apr 04.
DOI: 10.1002/gcc.23139
Abstrakt: NPM1 mutated non-AML myeloid neoplasms (MN; <20% blasts) are characterized by an aggressive clinical course in a few studies. In this retrospective study, we evaluate the clinicopathologic and immunohistochemical features of non-AML MN patients with NPM1 mutations. We assessed NPM1 mutation by targeted next generation sequencing (NGS). Cytoplasmic NPM1 expression was assessed by immunohistochemistry (IHC) on formalin-fixed, formic acid-decalcified bone marrow biopsy specimens. We evaluated 34 non-AML MN patients with NPM1 mutations comprising MDS (22), MPN (3) and MDS/MPN (9). They commonly presented with anemia (88%), thrombocytopenia (58%) and leukopenia (50%). Bone marrow dysplasia was common (79%). The karyotype was often normal (64%). NGS for MN-associated mutations performed in a subset of the patients showed a median of 3 mutations. NPM1 mutations were more often missense (c.859C > T p. L287F; 65%) than frameshift insertion/duplication (35%) with median variant allele frequency (VAF; 9.7%, range 5.1%-49.8%). Mutated NPM1 by IHC showed cytoplasmic positivity in 48% and positivity was associated with higher VAF. The median overall survival (OS) in this cohort was 70 months. Nine patients (26%) progressed to AML. OS in patients who progressed to AML was significantly shorter than the one of patients without progression to AML (OS 20 vs. 128 months, respectively, log rank p = 0.05). NPM1 mutated non-AML MN patients commonly had cytopenias, dysplasia, normal karyotype, mutations in multiple genes, and an unfavorable clinical outcome, including progression to AML. Our data demonstrated that IHC for NPM1 can be a useful supplementary tool to predict NPM1 mutation in some non-AML MN; however, genetic testing cannot be replaced by IHC assessment.
(© 2023 Wiley Periodicals LLC.)
Databáze: MEDLINE
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