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The assessment of Ki-67 as a prognostic marker in neuroendocrine tumours: a systematic review and meta-analysis
  1. Sebastian Richards-Taylor1,
  2. Sean M Ewings2,
  3. Eleanor Jaynes3,
  4. Charles Tilley3,
  5. Sarah G Ellis4,
  6. Thomas Armstrong5,
  7. Neil Pearce5,
  8. Judith Cave4
  1. 1Faculty of Medicine, University of Southampton, Southampton, UK
  2. 2Southampton Statistical Sciences Research Institute, University of Southampton, Southampton, UK
  3. 3Department of Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  4. 4Department of Medical Oncology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  5. 5Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  1. Correspondence to Dr Judith Cave, Department of Oncology, University Hospital NHS Foundation Trust, Tremona Road, Southampton, Hampshire SO166YD, UK; judith.cave{at}


Introduction Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are classified according to tumour mitotic count or Ki-67 labelling index (LI).

Aim(s) 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.

Method 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.


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