title: A comparison of Ki-67 and mitotic count as prognostic markers for metastatic pancreatic and midgut neuroendocrine neoplasms.
abstract: BACKGROUND
  The aim of this study was to compare mitotic count (MC) and Ki-67 proliferation index as prognostic markers in pancreatic and midgut neuroendocrine neoplasms (NENs).
  
  
  METHODS
  Two hundred eighty-five patients with metastatic NENs were recruited. Concordance between histological grade according to either Ki-67 or MC as defined by the European Neuroendocrine Tumour Society guidelines was assessed and the prognostic significance of Ki-67 or MC were evaluated.
  
  
  RESULTS
  There was a discrepancy of 44 and 38% in grade assignment when using Ki-67 or MC in pancreatic and midgut NENs, respectively. In multivariate analysis, grade using Ki-67, but not MC, was a significant prognostic factor in determining overall survival (hazard ratios: midgut G2 2.34, G3 15.1, pancreas G2 2.08, G3 11.3). The prognostic value of Ki-67 was improved using a modified classification (hazard ratios: midgut G2 3.02, for G3 22.1, pancreas G2 5.97, G3 33.8).
  
  
  CONCLUSIONS
  There is a lack of concordance between Ki-67 and MC in assigning tumour grade. Grade according to Ki-67 was a better prognostic marker than MC for metastatic pancreatic and midgut NENs. We suggest that Ki-67 alone should be used for grading pancreatic and midgut NENs and that the current threshold for classifying G1/G2 tumours should be revised from 2 to 5%.
authors.affiliation: Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital, London NW3 2QG, UK.
authors.forename: M S
authors.initials: MS
authors.lastname: Khan
authors.forename: T V
authors.initials: TV
authors.lastname: Luong
authors.forename: J
authors.initials: J
authors.lastname: Watkins
authors.forename: C
authors.initials: C
authors.lastname: Toumpanakis
authors.forename: M E
authors.initials: ME
authors.lastname: Caplin
authors.forename: T
authors.initials: T
authors.lastname: Meyer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011379:Prognosis; D013534:Survival; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen