title: [Clinicopathologic significance of bcl-6 gene rearrangement and expression in three molecular subgroups of diffuse large B-cell lymphoma].
abstract: OBJECTIVE
  To investigate the role of bcl-6 gene rearrangement and bcl-6 expression in three molecular subgroups of diffuse large B-cell lymphoma (DLBCL) and its clinicopathological significance.
  
  
  METHODS
  Tissue microarray including 163 newly diagnosed DLBCL was constructed. Fluorescence in situ hybridization (FISH) was performed to detect the bcl-6 gene rearrangement and immunohistochemistry (EnVision method) was used to evaluate the expression of bcl-6, Ki-67, cyclin D3, Geminin and P27(Kip1) proteins in DLBCL. The association with clinicopathological features was analyzed.
  
  
  RESULTS
  One hundred and forty nine of 163 cases were further classified into three molecular subgroups: 40 cases of germinal center B-cell-like (GCB) type, 75 cases of activated non-germinal center B-cell-like (ABC) type, 34 cases of Type 3. Of these 149 cases, FISH for bcl-6 gene rearrangement was successful in 118 cases. bcl-6 gene rearrangement was observed in 33 of 118 (28.0%) cases. The bcl-6 gene rearrangement was more frequently seen in the ABC subgroup (22/62, 35.5%) than in GCB (6/31, 19.4%) and Type 3 subgroups (5/25, 20.0%, P=0.16). The correlation of bcl-6 gene rearrangement and expression of its encoded protein was further analyzed. Most of DLBCL (26/33, 78.8%) with bcl-6 gene rearrangement presented with overexpression of its encoded protein, which was higher than those without bcl-6 gene rearrangement (53/84, 62.4%, P=0.088). DLBCL with bcl-6 gene rearrangement (24/33, 72.7%) more frequently expressed cyclin D3, and had a higher proliferative activity than those without bcl-6 gene rearrangement (37/81, 45.7% , P=0.009). Twenty-nine of 33 (87.9%) cases of DLBCL with bcl-6 gene rearrangement presented with advanced stage (Ann Arbor stage III/IV), which was higher than those without bcl-6 gene rearrangement (65/85, 76.5% , P=0.167). Univariate Cox proportional hazards regression analysis showed that bcl-6 gene rearrangement was associated with an increased relative risk (at 1.842) of death in DLBCL cases compared with those without bcl-6 gene rearrangement.
  
  
  CONCLUSIONS
  Overexpression of bcl-6 protein caused by bcl-6 gene rearrangement may play some important roles in the development and/or progression of a subset of DLBCL.
authors.affiliation: Department of Pathology and Laboratory Medicine, Guangdong Provincial People's Hospital, Guangzhou, 510080, China.
authors.forename: Fang-ping
authors.initials: FP
authors.lastname: Xu
authors.forename: Yan-hui
authors.initials: YH
authors.lastname: Liu
authors.forename: Xin-lan
authors.initials: XL
authors.lastname: Luo
authors.forename: Heng-guo
authors.initials: HG
authors.lastname: Zhuang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Dong-lan
authors.initials: DL
authors.lastname: Luo
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Fen
authors.initials: F
authors.lastname: Zhang
authors.forename: Ming-hui
authors.initials: MH
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Du
authors.forename: Wen-yu
authors.initials: WY
authors.lastname: Li
mesh_terms: D001402:B-Lymphocytes / Q000473:pathology; D002883:Chromosomes, Human, Pair 14; D056743:Cyclin D3 / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D056743:Cyclin D3; D051560:Proto-Oncogene Proteins c-bcl-6