title: MYC protein expression in primary diffuse large B-cell lymphoma of the central nervous system.
abstract: Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a rare, aggressive subtype of DLBCL, the biology of which is poorly understood. Recent studies have suggested a prognostic role of MYC protein expression in systemic DLBCL, but little is known about the frequency and significance of MYC protein expression in CNS DLBCL. Hence, we investigated MYC protein expression profiles of CNS DLBCL and assessed the relationship between MYC expression and a variety of histopathologic, immunophenotypic, genetic, and clinical features. Fifty-nine CNS DLBCL diagnosed at our institution over the past 13 years were evaluated. The majority of cases (80%) showed centroblastic morphology, and 12 (20%) displayed a perivascular pattern of infiltration. According to the Hans criteria, 41 (69%) cases had a non-germinal center B-cell and 18 (31%) had a germinal center B-cell cell-of-origin (COO) phenotype. Mean MYC protein expression was 50% (median: 50%, range: 10-80%). Forty-three cases (73%) showed MYC overexpression (≥ 40%), and 35 (60%) showed MYC/BCL2 coexpression. MYC overexpression was seen in the single case harboring MYC translocation and in the cases showing increased copies of MYC (27%); however, no significant difference in mean MYC expression was seen between groups harboring or lacking MYC aberrations. In our series, age was associated with a significantly increased risk of death, and the perivascular pattern of infiltration was associated with a significantly increased risk of disease progression. Neither MYC expression (with or without BCL2 coexpression) nor other variables, including COO subtype were predictive of clinical outcome. Our findings indicate that the proportion of CNS DLBCL overexpressing MYC is higher compared to systemic DLBCL, and MYC overexpression appears to be independent of genetic MYC abnormalities. Thus, MYC expression and other immunophenotypic markers used for prognostication of systemic DLBCL might not apply to CNS DLBCL due to differences in disease biology.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, 10032, United States of America.
authors.forename: Kamraan Z
authors.initials: KZ
authors.lastname: Gill
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, 10032, United States of America.
authors.forename: Fabio
authors.initials: F
authors.lastname: Iwamoto
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, 10032, United States of America.
authors.forename: Ashleigh
authors.initials: A
authors.lastname: Allen
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, 10032, United States of America.
authors.forename: Daniela
authors.initials: D
authors.lastname: Hoehn
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, 10032, United States of America.
authors.forename: Vundavalli V
authors.initials: VV
authors.lastname: Murty
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, 10032, United States of America.
authors.forename: Bachir
authors.initials: B
authors.lastname: Alobeid
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, 10032, United States of America.
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D016543:Central Nervous System Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc