title: Ki-67 prognostic and therapeutic decision driven marker for pancreatic neuroendocrine neoplasms (PNENs): A systematic review.
abstract: 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.
authors.affiliation: Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Pezzilli
authors.affiliation: Pancreatic Surgery Unit, Department of Surgery, San Raffaele Hospital, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Partelli
authors.affiliation: Department of Gastroenterology, National Cancer Institute, Aviano, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Cannizzaro
authors.affiliation: Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Nico
authors.initials: N
authors.lastname: Pagano
authors.affiliation: Pancreatic Surgery Unit, Department of Surgery, San Raffaele Hospital, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Crippa
authors.affiliation: Pancreatic Surgery Unit, Department of Surgery, San Raffaele Hospital, Milan, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Pagnanelli
authors.affiliation: Pancreatic Surgery Unit, Department of Surgery, San Raffaele Hospital, Milan, Italy. Electronic address: falconi.massimo@hsr.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Falconi
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D000066491:Clinical Decision-Making; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000601:surgery; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
keywords: Immune system disease; Ki-67; Pancreatic neuroendocrine neoplasms; Prognosis; Staging