title: Phosphohistone H3 and Ki-67 labeling indices in cytologic specimens from well-differentiated neuroendocrine tumors of the gastrointestinal tract and pancreas: a comparative analysis using automated image cytometry.
abstract: BACKGROUND
  Ki-67 proliferation index was recently incorporated in the grading of neuroendocrine neoplasms (NENs) of the gastrointestinal tract (GIT) and pancreas. These are now divided into well-differentiated neuroendocrine tumors (WDNETs, grades 1 and 2) and poorly differentiated neuroendocrine carcinomas (grade 3). While Ki-67 is an established proliferation marker in NENs, phosphohistone H3 (PHH3), a newer marker of mitotic activity, is not.
  
  
  METHODS
  We determined Ki-67 and PHH3 indices on cytologic samples from WDNETs of the GIT and pancreas using an automated cellular imaging system (ACIS®).
  
  
  RESULTS
  There was a strong correlation between Ki-67 and PHH3 indices generated by ACIS on cytologic samples. However, in some cases the two stains caused conflicting grades within the same tumor.
  
  
  CONCLUSIONS
  Both antibodies stain cells in different phases of the cell cycle which may cause discordant grades, thus affecting patient management and prognostication. Ki-67 staining is stronger than PHH3, making 'hot spots' easier to identify on ACIS. Ki-67 is more ideal than PHH3 for staining NENs, especially in tumors with borderline grades. Because PHH3 generates lower mitotic indices it should not be used as a proliferation marker in NENs until its expression has been further characterized.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, Ga., USA.
authors.forename: Adele D
authors.initials: AD
authors.lastname: Fung
authors.forename: Cynthia
authors.initials: C
authors.lastname: Cohen
authors.forename: Sravankumar
authors.initials: S
authors.lastname: Kavuri
authors.forename: Diane
authors.initials: D
authors.lastname: Lawson
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Reid
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D044963:Biopsy, Fine-Needle; D002454:Cell Differentiation; D049109:Cell Proliferation; D003581:Cytodiagnosis; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis* / Q000473:pathology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D019044:Image Cytometry; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D010766:Phosphorylation
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones; D019394:Ki-67 Antigen