title: The value of the Ki-67 proliferation marker as a prognostic factor in gastroenteropancreatic neuroendocrine tumours.
abstract: BACKGROUND
  Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are a heterogenous group of tumours of various clinical presentations. Proliferative activity of tumour cells is an essential parameter determining the course of the disease and affecting the prognosis. The Ki-67 antigen is an important marker of cell proliferation, which shows activity in all the phases of the cell cycle, excluding the G0 phase.
  
  
  OBJECTIVE
  To assess the expression of Ki-67 in GEP NETs and to examine the association of Ki-67 with the stage of the tumour (tumour size, presence of metastases) and the hormonal function of the tumour.
  
  
  METHODS
  We included 61 patients with GEP NETs (25 males and 36 females aged between 20 and 82 years [mean age: 56 years]). The proliferative activity was examined in paraffin blocks containing surgically removed tumour samples and in core-needle biopsies of primary and metastatic tumours. The presence of the Ki-67 antigen was assessed by immunohistochemistry using MIB‑1 monoclonal antibodies. Based on the Ki-67 proliferative index we determined the tumour grade. In addition, we determined the tumour stage according to the TNM classification. In all the subjects we determined the levels of the non-specific NET marker (chromogranin A) and of specific NET markers (serotonin, insulin and gastrin in the blood and 5‑hydroxyindoleacetic acid [5‑HIAA] in 24-hour urine).
  
  
  RESULTS
  The diagnoses of low-grade (Ki‑67 ≤ 2%), intermediate-grade (Ki-67 3-20%) and high-grade (Ki‑67 > 20%) NET were established in 38, 12 and 11 patients, respectively. Metastatic disease was diagnosed in 36/61 patients. A significantly higher expression of K-67 was observed in patients with metastatic disease (p = 0.01). A positive correlation was demonstrated between Ki-67 and the stage of the disease (p = 0.01) and between the histologic grade of the tumour and the stage of the disease (p = 0.01). No association between Ki-67 and the levels of chromogranin A, serotonin, insulin, gastrin and 5-HIAA was shown. There was also no difference in Ki-67 expression relative to the location of the primary tumour and the tumour size.
  
  
  CONCLUSIONS
  The Ki-67 proliferative index is an essential parameter predicting the course of GEP-NETs.
authors.affiliation: Department of Endocrinology, Division of Pathophysiology and Endocrinology, Silesian Medical University, Katowice, Poland. wandafoltyn@poczta.onet.pl
authors.forename: Wanda
authors.initials: W
authors.lastname: Foltyn
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zajęcki
authors.forename: Bogdan
authors.initials: B
authors.lastname: Marek
authors.forename: Dariusz
authors.initials: D
authors.lastname: Kajdaniuk
authors.forename: Lucyna
authors.initials: L
authors.lastname: Siemińska
authors.forename: Anna
authors.initials: A
authors.lastname: Zemczak
authors.forename: Beata
authors.initials: B
authors.lastname: Kos-Kudła
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen