title: Low nuclear proliferative activity is associated with nonmetastatic islet cell tumors.
abstract: BACKGROUND
  Traditional morphologic features of tumor aggression are of limited value in predicting the malignant behavior of endocrine neoplasms. We explored the potential value of nuclear proliferative activity (using Ki-67 immunostaining with semiquantitative scoring) in predicting the clinical behavior of pancreatic islet cell tumors (ICTs), and we correlated this characteristic with hormone expression.
  
  
  OBJECTIVE
  To evaluate whether Ki-67 immunostaining using a semiquantitative scoring system has value in predicting the clinical behavior of pancreatic ICTs.
  
  
  METHODS
  We studied 39 pancreatic ICTs from 39 patients. Twenty-two ICTs did not metastasize in a median follow-up period of 91 months. The remaining 17 neoplasms did produce metastases (8 in liver, 7 in regional lymph nodes, and 2 in peritoneum). Immunohistochemistry was performed using antibodies to Ki-67 and pancreatic hormones (insulin, glucagon, gastrin, somatostatin, pancreatic polypeptide, vasoactive intestinal polypeptide, and corticotropin). A semiquantitative Ki-67 grading system was followed. The nuclear proliferative activity, as determined by a positive reaction for Ki-67, was considered low (<5% of cells staining positively), intermediate (5%-25% of cells staining positively), or high (>25% of cells staining positively).
  
  
  RESULTS
  The majority of the nonmetastatic ICTs (16 cases, 73%) demonstrated either negative or low staining for Ki-67 (P <.001). Conversely, all metastatic ICTs expressed at least an intermediate-grade reaction. High nuclear proliferative activity was only seen in metastatic neoplasms (3 cases, 17%). There was no relationship between immunoexpression of pancreatic hormones and nuclear proliferative activity by either group of tumors.
  
  
  CONCLUSIONS
  An ICT with low nuclear proliferative activity is unlikely to metastasize, whereas high proliferative activity is associated with a metastatic phenotype. Immunohistochemical assessment of Ki-67 using a semiquantitative scoring system is a simple and reliable detection method of cellular proliferative activity in ICTs of the pancreas.
authors.affiliation: Department of Pathology, University of Miami, Jackson Memorial Medical Center, Miami, FL 33136, USA. mjorda@med.miami.edu
authors.forename: Merce
authors.initials: M
authors.lastname: Jorda
authors.forename: Zeina
authors.initials: Z
authors.lastname: Ghorab
authors.forename: Gustavo
authors.initials: G
authors.lastname: Fernandez
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nassiri
authors.forename: Andrew
authors.initials: A
authors.lastname: Hanly
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Nadji
mesh_terms: D000328:Adult; D000368:Aged; D018273:Carcinoma, Islet Cell / Q000737:chemistry / Q000473:pathology* / Q000556:secondary*; D002455:Cell Division; D002467:Cell Nucleus / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019394:Ki-67 Antigen / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010187:Pancreatic Hormones / Q000276:immunology / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000473:pathology*; D010641:Phenotype; D011237:Predictive Value of Tests
chemical_list: D019394:Ki-67 Antigen; D010187:Pancreatic Hormones