title: [Clinical characteristics and prognosis of concurrent positive t(14; 18) and myc gene rearrangement in diffuse large B cell lymphoma].
abstract: OBJECTIVE
  To study the incidence of positive t(14; 18) and myc gene rearrangement, and the clinical features and prognosis of concurrent positive t(14; 18) and myc gene rearrangement "double-hit lymphoma" (DHL) in diffuse large B cell lymphoma.
  
  
  METHODS
  The positive t(14; 18) and myc gene rearrangement in 106 cases of DLBCL were analyzed using interphase fluorescent in situ hybridization (FISH) technique. The expression of myc and bcl-2 proteins was determined by immunohistochemistry. The relationship of positive t(14; 18) and myc gene rearrangement with clinical features, pathogenesis and prognosis for the patients was analyzed. SPSS 16.0 software was used for statistical analysis.
  
  
  RESULTS
  Among the 106 cases, there were 27 (25.5%) cases with positive t(14; 18) and 13 (12.3%) cases with myc gene rearrangement, and 7 cases (6.6%) of DLBCL with concurrent t(14; 18)-positive and myc gene rearrangement. A relationship was observed between positive t(14; 18) and myc gene rearrangement (P=0.019). The follow-up data showed that the 7 DHL patients were in age of 52-84 years, the International Prognostic Index (IPI) scores were 3 in two cases, 4 in four cases and 5 in one case, and the ECOG scores were 3 in all the 7 cases. Four patients had bone marrow involvement and were combined with leukemia. The survival time ranged from 0.5 to 6 months, with a median survival of 4 months. The univariate analysis showed that B symptom, Ann Arbor stage, ECOG score, LDH level, IPI score, immunophenotype, bcl-2 protein expression, myc protein expression, and myc gene rearrangement were all associated with poor prognosis (P<0.05 for all). The multivariate analysis using a COX proportional hazard model confirmed that ECOG score, bcl-2 protein expression, myc protein expression, myc gene rearrangement, and immunophenotype were independent prognostic factors affecting survival (P<0.05 for all), among them, the myc gene rearrangement was the strongest prognostic factor (OR=4.337, P<0.001).
  
  
  CONCLUSIONS
  "Double-hit" DLBCL is rare and can be mainly identified only by molecular detection. Perhaps positive t(14; 18) and myc gene rearrangement play concurrent role in its "double-hit" pathogenesis. DHL are highly invasive, and most of DHL patients have poor prognosis. Further studies of larger case number are required to determine the pathologic features and the therapeutic strategy of this subgroup.
authors.affiliation: Department of Hematology, Shanxi Tumor Hospital, Taiyuan 030013, China.
authors.forename: H W
authors.initials: HW
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Fenyang College, Shanxi Medical University, Fenyang 032200, China.
authors.forename: Z W
authors.initials: ZW
authors.lastname: Chen
authors.affiliation: Department of Hematology, Shanxi Tumor Hospital, Taiyuan 030013, China.
authors.forename: L Y
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Department of Hematology, Shanxi Tumor Hospital, Taiyuan 030013, China.
authors.forename: J X
authors.initials: JX
authors.lastname: He
authors.affiliation: Department of Hematology, Shanxi Tumor Hospital, Taiyuan 030013, China.
authors.forename: Y P
authors.initials: YP
authors.lastname: Zheng
authors.affiliation: Department of Hematology, Shanxi Tumor Hospital, Taiyuan 030013, China.
authors.forename: W E
authors.initials: WE
authors.lastname: Han
authors.affiliation: Department of Hematology, Shanxi Tumor Hospital, Taiyuan 030013, China.
authors.forename: B
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Hematology, Shanxi Tumor Hospital, Taiyuan 030013, China.
authors.forename: Y L
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Department of Hematology, Shanxi Tumor Hospital, Taiyuan 030013, China.
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Zhao
authors.affiliation: Department of Hematology, Shanxi Tumor Hospital, Taiyuan 030013, China.
authors.forename: M
authors.initials: M
authors.lastname: Bai
authors.affiliation: Department of Hematology, Shanxi Tumor Hospital, Taiyuan 030013, China.
authors.forename: L P
authors.initials: LP
authors.lastname: Su
mesh_terms: D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D015321:Gene Rearrangement; D016259:Genes, myc; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc