title: High Ki-67 expression in diffuse large B-cell lymphoma patients with non-germinal center subtype indicates limited survival benefit from R-CHOP therapy.
abstract: OBJECTIVE
  Rituximab has significantly improved the survival of patients with DLBCL, especially those with non-germinal center B-cell-like (non-GCB) subtype. The impact of Ki-67 expression, an index of proliferation, on the clinical outcomes of patients with DLBCL has largely been unexplored. This study aimed to investigate whether Ki-67 expression is an indicator of outcome in DLBCL patients (especially non-GCB DLBCL patients) treated with standard chemotherapy combined with rituximab.
  
  
  METHODS
  Expression of Ki-67 protein was examined immunohistochemically in 118 tumor specimens from patients newly diagnosed with DLBCL and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).
  
  
  RESULTS
  Overall survival (OS) and progression-free survival (PFS) were lower in patients with high Ki-67 expression than in those with low Ki-67 expression (3-year OS: 65.2% vs. 81.7%, P = 0.030; 3-year PFS: 56.4% vs. 73.3%, P = 0.020), similar in patients with GCB subtype and those with the non-GCB subtype (OS: P = 0.330; PFS: P = 0.287). According to Ki-67 expression status by immunophenotype subgroups, patients with high Ki-67 expression in non-GCB subgroup had the most unfavorable PFS and OS, comparing with the other three subgroups (P = 0.004 and P = 0.002, respectively). In multivariate analysis, non-GCB with high Ki-67 expression was an independent prognostic predictor of inferior survival in DLBCL patients treated with R-CHOP.
  
  
  CONCLUSIONS
  For DLBCL patients with non-GCB DLBCL and high Ki-67 expression, the survival benefit from R-CHOP therapy is limited.
authors.affiliation: State Key Laboratory of Oncology in Southern China, Sun Yat-sen University, Guangzhou, Guangdong, China. lzmlzmlzm@yahoo.com
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Li
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Huang
authors.forename: Yi
authors.initials: Y
authors.lastname: Xia
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Wen-Xiao
authors.initials: WX
authors.lastname: Wei
authors.forename: Wen-Qi
authors.initials: WQ
authors.lastname: Jiang
authors.forename: Tong-Yu
authors.initials: TY
authors.lastname: Lin
authors.forename: Hui-Qiang
authors.initials: HQ
authors.lastname: Huang
authors.forename: Zhong-Zhen
authors.initials: ZZ
authors.lastname: Guan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D012189:Retrospective Studies; D000069283:Rituximab; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D019394:Ki-67 Antigen; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone