title: The assessment of Ki-67 as a prognostic marker in neuroendocrine tumours: a systematic review and meta-analysis.
abstract: BACKGROUND
  Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are classified according to tumour mitotic count or Ki-67 labelling index (LI).
  
  
  OBJECTIVE
  To systematically review articles reporting the prognosis of patients by Ki-67 LI and thereby improve the ability of clinicians to prognosticate for their patients.
  
  
  METHODS
  265 abstracts were identified relating Ki-67 and survival. After exclusion criteria were applied, 22 articles remained. Articles were excluded if they described non-human specimens, were non-English language, published prior to 2000, reported non-GEP NETs, reported subgroups selected by treatment modality or included <20 cases. Random-effects meta-analysis was used to combine studies to estimate survival proportions.
  
  
  RESULTS
  Authors used varied methods in which to present 5-year survival, with often limited survival information. This reduced the number of studies that could be included in the meta-analysis. 5-year survival for patients with grade 1 and 2 GEP NETs were estimated to be 89% (95% CI 85% to 92%, m=12 studies, n=977 participants) and 70% (95% CI 62% to 79%, m=9, n=726), respectively. Using an alternative grade 1/2 boundary of 5%, 5-year survival rates for Ki-67≤5% and 5-20% were estimated as 89% (95% CI 84% to 94%, m=7, n=654) and 51% (95% CI 44% to 59%, m=4, n=183), respectively. For Ki-67>20%, 5-year survival was estimated to be 25% (95% CI 12% to 38%, m=10, n=208).
  
  
  CONCLUSIONS
  Standardisation of grade boundaries has allowed us to combine data from multiple studies and amass a body of evidence linking Ki-67 and survival.
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Richards-Taylor
authors.affiliation: Southampton Statistical Sciences Research Institute, University of Southampton, Southampton, UK.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Ewings
authors.affiliation: Department of Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Jaynes
authors.affiliation: Department of Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Tilley
authors.affiliation: Department of Medical Oncology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Ellis
authors.affiliation: Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Armstrong
authors.affiliation: Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Pearce
authors.affiliation: Department of Medical Oncology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Judith
authors.initials: J
authors.lastname: Cave
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D018572:Disease-Free Survival; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008940:Mitotic Index; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
keywords: DEATH; NEUROENDOCRINE TUMOURS; STAINING