title: Computerized image analysis of the Ki-67 proliferation index in mantle cell lymphoma.
abstract: OBJECTIVE
  Manual counting of the fraction of Ki-67-positive cells (the Ki-67 index) in 1000 tumour cells is considered the 'gold standard' to predict prognosis in mantle cell lymphoma (MCL). This time-consuming method is replaced by the faster, but less accurate, semiquantitative estimation in routine practice. The aim of this study was to investigate the use of computerized image analysis software for scoring of Ki-67 in MCL.
  
  
  RESULTS
  We developed an automated method for determining the Ki-67 index by computerized image analysis and tested it using a cohort of 62 MCL patients. The data were compared to Ki-67 scores obtained by semiquantitative estimation and image-based manual counting. When using the Ki-67 index as a continuous parameter, both image-based manual counting and computerized image analysis were related inversely to survival (P = 0.020 and P = 0.025, respectively). Ki-67 index obtained by semiquantitative estimation was not associated significantly with survival (P = 0.093). The results were validated in a second patient cohort with similar results.
  
  
  CONCLUSIONS
  Computerized image analysis of the Ki-67 index in MCL is an attractive alternative to semiquantitative estimation and can be introduced easily in a routine diagnostic setting for risk stratification in MCL.
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Yngvild N
authors.initials: YN
authors.lastname: Blaker
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.|Department of Oncology, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Oslo, Norway.
authors.forename: Marianne
authors.initials: M
authors.lastname: Brodtkorb
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.
authors.forename: John
authors.initials: J
authors.lastname: Maddison
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.|Department of Informatics, University of Oslo, Oslo, Norway.
authors.forename: Tarjei S
authors.initials: TS
authors.lastname: Hveem
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.
authors.forename: John Arne
authors.initials: JA
authors.lastname: Nesheim
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.
authors.forename: Hans Martin
authors.initials: HM
authors.lastname: Mohn
authors.affiliation: Department of Oncology, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Kolstad
authors.affiliation: Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christian H
authors.initials: CH
authors.lastname: Geisler
authors.affiliation: Department of Informatics, University of Oslo, Oslo, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Liestøl
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Erlend B
authors.initials: EB
authors.lastname: Smeland
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Oncology, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Oslo, Norway.
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.affiliation: Department of Pathology, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Oslo, Norway.|Department of Pathology, University of Toronto, Toronto, Canada.
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.|Department of Informatics, University of Oslo, Oslo, Norway.|Nuffield Division of Clinical and Laboratory Sciences, University of Oxford, Oxford, UK.
authors.forename: Håvard
authors.initials: H
authors.lastname: Danielsen
mesh_terms: D002452:Cell Count; D049109:Cell Proliferation; D015331:Cohort Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D019394:Ki-67 Antigen / Q000378:metabolism*; D020522:Lymphoma, Mantle-Cell / Q000378:metabolism* / Q000473:pathology*
chemical_list: D019394:Ki-67 Antigen
keywords: Ki-67 antigen; computer-assisted image analysis; malignant lymphoma; mantle cell lymphoma