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

Acta Cytol. 2013;57(3):291-5. doi: 10.1159/000350885. Epub 2013 Apr 25.

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).

Study design: 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.

Publication types

  • Evaluation Study

MeSH terms

  • Biopsy, Fine-Needle / methods*
  • Histones / analysis*
  • Humans
  • Image Interpretation, Computer-Assisted*
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Mitotic Index*
  • Neoplasm Grading
  • Pancreatic Neoplasms / chemistry
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / pathology
  • Phosphoproteins / analysis*
  • Predictive Value of Tests
  • Retrospective Studies

Substances

  • Histones
  • Ki-67 Antigen
  • Phosphoproteins