title: Cell cycle regulation score predicts relapse-free survival in non-germinal centre diffuse large B-cell lymphoma patients treated by means of immunochemotherapy.
abstract: OBJECTIVE
  The cell cycle is under strict regulation by the retinoblastoma, p53 and p27 pathways, and the disruption of these pathways is an important characteristic of diffuse large B-cell lymphoma (DLBCL). In this study, we wanted to assess the function and prognostic significance of these pathways in DLBCL patients.
  
  
  METHODS
  Tissue samples from 120 DLBCL patients treated by means of R-CHOP-type chemotherapy were stained for the cell cycle-regulating proteins p16, p21, p27 and p53, and the germinal centre (GC) phenotype was determined according to Hans' algorithm. Based on the number of impaired cell cycle-regulating pathways a predictive score was obtained, covering three different prognostic groups: a 'favourable' group with damage in 0-1 of the studied pathways, a 'poor' group with damage in all three pathways and an 'intermediate' group comprising the rest of the patients.
  
  
  RESULTS
  The prognosis of non-GC DLBCL patients was significantly poorer vs. GC phenotype patients (P = 0.015). The prognostic score proved especially useful among non-GC phenotype patients, with 3-yrs relapse-free survival of 100% vs. 62.6% vs. 24.3% in the 'favourable-', 'intermediate-' and 'poor prognosis' groups, respectively (P = 0.003).
  
  
  CONCLUSIONS
  The prognosis of non-GC DLBCL patients is progressively impaired with the accumulation of damage in different cell cycle-regulating pathways.
authors.affiliation: Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, Oulu, Finland. pasaanna@mail.student.oulu.fi
authors.forename: Anna Kaisa
authors.initials: AK
authors.lastname: Pasanen
authors.forename: Kirsi-Maria
authors.initials: KM
authors.lastname: Haapasaari
authors.forename: Jenni
authors.initials: J
authors.lastname: Peltonen
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
authors.forename: Esa
authors.initials: E
authors.lastname: Jantunen
authors.forename: Risto
authors.initials: R
authors.lastname: Bloigu
authors.forename: Taina
authors.initials: T
authors.lastname: Turpeenniemi-Hujanen
authors.forename: Outi
authors.initials: O
authors.lastname: Kuittinen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D002453:Cell Cycle; D003131:Combined Modality Therapy / Q000379:methods; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D012008:Recurrence; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C583516:p12(INK4a) protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27