title: Grading of neuroendocrine neoplasms: mitoses and Ki-67 are both essential.
abstract: BACKGROUND
  The current WHO classification for neuroendocrine neoplasms (NEN) of the gastrointestinal tract requires Ki-67 and mitotic index for grading. However, both indexes might be conflicting as far as grade is concerned. In this study, we investigate which of the two indexes is most informative to predict survival.
  
  
  METHODS
  We assessed 362 patients with NEN of gastrointestinal (n = 148), pancreatic (n = 29), lung (n = 77), unknown primary site (n = 102) and of miscellaneous (n = 6) origin. Follow-up and proliferative indexes were recorded.
  
  
  RESULTS
  Survival was clearly correlated with both proliferative indexes (p < 0.001). One hundred and nineteen samples (34%) showed discordance in grading between the Ki-67 and the mitotic index, of which 74 (62%) were biopsies and 45 (38%) resection specimens (p = 0.001). In 86% of these cases, survival matched with the highest proliferative index, which was the Ki-67 index in 87% of these cases. Seventeen cases had a mitotic index of 2 (threshold grade 2) and a Ki-67 index of <3% (grade 1). For these cases, survival curve matched that of patients with concordant indexes of grade 1.
  
  
  CONCLUSIONS
  Grading NEN using two proliferative markers results in discordance between these indexes in one third of cases, more often in biopsy material than in resection specimens. If results are discordant, survival is for the most part associated with the grade of the highest index, for the most part Ki-67. Thus, grading with two proliferative indexes is useful as it highlights cases where one of these indexes may be incongruent.
authors.affiliation: Department of Pathology, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Marie-Louise F
authors.initials: ML
authors.lastname: van Velthuysen
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Groen
authors.forename: Vincent
authors.initials: V
authors.lastname: van der Noort
authors.forename: Arjen
authors.initials: A
authors.lastname: van de Pol
authors.forename: Margot E T
authors.initials: ME
authors.lastname: Tesselaar
authors.forename: Catharina M
authors.initials: CM
authors.lastname: Korse
mesh_terms: D005260:Female; D005500:Follow-Up Studies; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008938:Mitosis / Q000502:physiology*; D060787:Neoplasm Grading / Q000379:methods*; D009382:Neoplasms, Unknown Primary / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D016019:Survival Analysis
chemical_list: D019394:Ki-67 Antigen