Ki-67 prognostic and therapeutic decision driven marker for pancreatic neuroendocrine neoplasms (PNENs): A systematic review

Adv Med Sci. 2016 Mar;61(1):147-53. doi: 10.1016/j.advms.2015.10.001. Epub 2015 Oct 23.


Background: We systematically evaluate the current evidence regarding Ki-67 as a prognostic factor in pancreatic neuroendocrine neoplasms to evaluate the differences of this marker in primary tumors and in distant metastases as well as the values of Ki-67 obtained by fine needle aspiration and by histology.

Methods: The literature search was carried out using the MEDLINE/PubMed database, and only papers published in the last 10 years were selected.

Results: The pancreatic tissue suitable for Ki-67 evaluation was obtained from surgical specimens in the majority of the studies. There was a concordance of 83% between preoperative and postoperative Ki-67 evaluation. Pooling the data of the studies which compared the Ki-67 values obtained in both cytological and surgical specimens, we found that they were not related. The assessment of Ki-67 was manual in the majority of the papers considered for this review. In order to eliminate manual counting, several imaging methods have been developed but none of them are routinely used at present. Twenty-two studies also explored the role of Ki-67 utilized as a prognostic marker for pancreatic neuroendocrine neoplasms and the majority of them showed that Ki-67 is a good prognostic marker of disease progression. Three studies explored the Ki-67 value in metastatic sites and one study demonstrated that, in metachronous and synchronous liver metastases, there was no significant variation in the index of proliferation.

Conclusions: Ki-67 is a reliable prognostic marker for pancreatic neuroendocrine neoplasms.

Keywords: Immune system disease; Ki-67; Pancreatic neuroendocrine neoplasms; Prognosis; Staging.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Clinical Decision-Making*
  • Humans
  • Ki-67 Antigen / metabolism*
  • Neuroendocrine Tumors / metabolism*
  • Neuroendocrine Tumors / surgery
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / surgery
  • Prognosis


  • Biomarkers, Tumor
  • Ki-67 Antigen