title: MYC cytogenetic status correlates with expression and has prognostic significance in patients with MYC/BCL2 protein double-positive diffuse large B-cell lymphoma.
abstract: MYC/BCL2 double-hit lymphoma (DHL), defined by conventional cytogenetic or fluorescence in situ hybridization (FISH) analysis, and MYC/BCL2 double-positive lymphoma (DPL), defined by immunohistochemistry, are associated with a poor prognosis. However, DHL and DPL are not concordant, and it is unclear whether MYC and BCL2 aberrations have prognostic impact in DPL patients. In a cohort of 135 patients diagnosed with large B-cell lymphoma between 2010 and 2014 in whom MYC/8q24 and BCL2/t(14;18)(q32;q21) statuses were assessed by FISH at diagnosis, we evaluated MYC and BCL2 expression by immunohistochemistry. A total of 54 (40%) cases were positive for MYC and BCL2 supporting DPL. Among them, 19 (35%) had MYC rearrangement including 11 DHLs, 12 (22%) had multiple copies of MYC, 19 had no MYC abnormalities, and in 4 cases FISH analysis failed. BCL2 abnormalities were present in 28/54 (52%) cases (20 rearranged and 8 multiple copies). MYC rearrangement correlated with a significantly worse overall survival in DPL (P<0.05), whereas BCL2 genetic status did not correlate with survival (P>0.05). MYC and BCL2 expression by immunohistochemistry correlates with gene status by FISH; however, immunohistochemistry is neither specific nor adequately sensitive to be used as a surrogate for MYC and BCL2 gene status using any cutoff level. In conclusion, MYC rearrangement identifies a subset of patients with DPL who have a significantly worse prognosis. Although immunohistochemical assessment for MYC and BCL2 may be a helpful initial screen to identify higher-risk patients, FISH analysis for MYC remains important for further risk stratification in patients with DPL.
authors.affiliation: *Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN †Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Xuan Julia
authors.initials: XJ
authors.lastname: Wang
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Pei
authors.initials: P
authors.lastname: Lin
authors.forename: C Cameron
authors.initials: CC
authors.lastname: Yin
authors.forename: Shimin
authors.initials: S
authors.lastname: Hu
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Thompson
authors.forename: Shaoying
authors.initials: S
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000235:genetics*; D015203:Reproducibility of Results; D013997:Time Factors; D055815:Young Adult
chemical_list: C000595707:BCL2 protein, human; D014408:Biomarkers, Tumor; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc