title: High-grade B-cell Lymphoma With MYC Rearrangement and Without BCL2 and BCL6 Rearrangements Is Associated With High P53 Expression and a Poor Prognosis.
abstract: Patients with MYC/BCL2 double-hit lymphoma (DHL) are known to have an aggressive clinical course and to respond poorly to various therapies including intensive chemotherapy and stem cell transplant. Less is known about high-grade B-cell lymphoma with MYC rearrangement without concomitant BCL2 and BCL6 rearrangement, designated here as single-hit lymphoma (SHL). In this study, we assessed 61 cases of SHL and compared them with 83 cases of DHL, all confirmed by MYC, BCL2, and BCL6 fluorescence in situ hybridization studies. Although many clinicopathologic features overlap between patients with SHL and those with DHL, distinct features were observed in SHL. Patients with SHL had tumors with a higher prevalence of p53 overexpression (P=0.047), less frequent expression of CD10, BCL2, and BCL6 (P<0.05), and less often had a history of low-grade B-cell lymphoma (P=0.01). In addition, MYC was more frequently partnered with IGH in SHL than in DHL (P=0.04). With a median follow-up of 25 months, the overall survival of 61 SHL patients was poor and similar to that of DHL patients (2-y overall survival rate of 41% in SHL vs. 48% in DHL; P=0.35) and significantly worse than patients with diffuse large B-cell lymphoma and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, without MYC and BCL2 rearrangements (P<0.0001). In conclusion, patients with SHL have distinct clinicopathologic features but a similar poor prognosis compared with patients with MYC/BCL2 DHL. The poor prognosis of patients with SHL may be partially related to the higher frequency and level of p53 expression in these tumors.
authors.affiliation: Departments of *Pathology‡Hematology/Oncology, Vanderbilt University School of Medicine, Nashville, TN†Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Shaoying
authors.initials: S
authors.lastname: Li
authors.forename: Vivian L
authors.initials: VL
authors.lastname: Weiss
authors.forename: Xuan J
authors.initials: XJ
authors.lastname: Wang
authors.forename: Parth A
authors.initials: PA
authors.lastname: Desai
authors.forename: Shimin
authors.initials: S
authors.lastname: Hu
authors.forename: C Cameron
authors.initials: CC
authors.lastname: Yin
authors.forename: Guilin
authors.initials: G
authors.lastname: Tang
authors.forename: Nishitha M
authors.initials: NM
authors.lastname: Reddy
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Pei
authors.initials: P
authors.lastname: Lin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D001706:Biopsy; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D016393:Lymphoma, B-Cell / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D010641:Phenotype; D011237:Predictive Value of Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012307:Risk Factors; D013714:Tennessee; D013781:Texas; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C000595707:BCL2 protein, human; C084103:BCL6 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53