title: Reliability of proliferation assessment by Ki-67 expression in neuroendocrine neoplasms: eyeballing or image analysis?
abstract: BACKGROUND
  The latest WHO classification for neuroendocrine neoplasms (NEN) of the gastrointestinal tract defines grade according to Ki-67 and mitotic indices. Some have questioned the reproducibility and thus the reliability of Ki-67 assessment. We therefore investigated the accuracy of this proliferation marker in NEN.
  
  
  METHODS
  The Ki-67 index of tumor specimens of NEN (n = 73) was assessed by two pathologists as in routine practice with eyeballing and twice by image analysis using ImageJ freeware at different magnifications. RESULTS were correlated with overall survival.
  
  
  RESULTS
  The intraclass correlation coefficient (ICC) between pathologists was 0.88. The ICC for the measurements using image analysis was 0.85. The ICC between all four measurements (pathologists and ImageJ) was 0.80. If the Ki-67 index was translated to grade as prescribed by the current WHO classification (<3% = grade 1, 3-20% = grade 2, >20% = grade 3), kappa was between 0.61 and 0.75. Grades based on pathologist scoring were often (16-29%) higher than grades assigned by image analysis (p < 0.001). Grade was significantly correlated with survival (p < 0.0001) irrespective of the way Ki-67 was assessed.
  
  
  CONCLUSIONS
  Assessment of the Ki-67 index by eyeballing correlates remarkably well with the Ki-67 index as calculated by image analysis and is therefore an accurate parameter. Moreover, it is significantly related to survival irrespective of the method used. Yet if the Ki-67 index is translated to grade, the grade should be interpreted with caution due to values around threshold levels.
authors.affiliation: Department of Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Marie-Louise F
authors.initials: ML
authors.lastname: van Velthuysen
authors.forename: Emilie J
authors.initials: EJ
authors.lastname: Groen
authors.forename: Joyce
authors.initials: J
authors.lastname: Sanders
authors.forename: Frans A
authors.initials: FA
authors.lastname: Prins
authors.forename: Vincent
authors.initials: V
authors.lastname: van der Noort
authors.forename: Catharina M
authors.initials: CM
authors.lastname: Korse
mesh_terms: D049109:Cell Proliferation; D003952:Diagnostic Imaging / Q000379:methods / Q000592:standards*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D018358:Neuroendocrine Tumors / Q000175:diagnosis* / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D019394:Ki-67 Antigen