title: The potential value of phosphohistone-h3 mitotic index determined by digital image analysis in the assessment of pancreatic endocrine tumors in fine-needle aspiration cytology specimens.
abstract: OBJECTIVE
  According to the World Health Organization, pancreatic endocrine tumors are graded by assessment of the Ki67 proliferation index and/or mitotic count. The objective was to find comparable grading on the basis of the novel mitotic marker phosphohistone-H3 (PHH3).
  
  
  METHODS
  A computer-assisted system was used to assess 23 cell blocks stained with PHH3 and Ki67 antibodies. We investigated possible cut-points for PHH3 and computed percent agreement between the PHH3- and Ki67-based grading.
  
  
  RESULTS
  The Spearman correlation between percent Ki67 positive and percent PHH3 positive was 0.76 (p = 0.001). A value of 0.3% for the lower cut-point ('cut-point 1', differentiating between grades 1 and 2) and values of about 1.8-1.9% for the higher cut-point ('cut-point 2', differentiating between grades 2 and 3) shows optimal agreement between PHH3 and Ki67 grading. The percentage of positive cells was much higher for Ki67 than for PHH3 (mean 10.6 vs. 3.0%).
  
  
  CONCLUSIONS
  PHH3 has good correlation with Ki67, but the range of PHH3 positivity is much narrower than that of Ki67 (range 0-4% for PHH3 vs. 0-50% for Ki67). Therefore, to be as accurate, grading on the basis of PHH3 requires evaluation of a larger number of tumor cells for a precise determination of percent PHH3-positive nuclei.
authors: Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Philadelphia, Pa. 19107, USA. rossitza.draganova-tacheva@jefferson.edu
authors: Rossitza
authors: R
authors: Draganova-Tacheva
authors: Marluce
authors: M
authors: Bibbo
authors: Ruth
authors: R
authors: Birbe
authors: Constantine
authors: C
authors: Daskalakis
authors: Charalambos
authors: C
authors: Solomides
mesh_terms: D044963:Biopsy, Fine-Needle / Q000379:methods*; D006657:Histones / Q000032:analysis*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008940:Mitotic Index; D060787:Neoplasm Grading; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000473:pathology; D010750:Phosphoproteins / Q000032:analysis*; D011237:Predictive Value of Tests; D012189:Retrospective Studies
chemical_list: D006657:Histones; D019394:Ki-67 Antigen; D010750:Phosphoproteins