Tumor proliferative fraction in solid malignant neoplasms. A comparative study of Ki-67 immunostaining and flow cytometric determinations

Am J Clin Pathol. 1991 Oct;96(4):512-9. doi: 10.1093/ajcp/96.4.512.


Tumor proliferative fraction (TPF) has been shown to correlate with prognosis in some malignancies. A method for its determination that is practical, accurate, and reproducible is still being sought. In this comparative study of techniques, TPF values were determined in mirror-image samples of 126 consecutive solid malignant neoplasms using flow cytometry and immunostaining with Ki-67, a monoclonal antibody that recognizes an unknown nuclear antigen expressed during the entire cell proliferation cycle but not in resting cells. The mean TPF values for all cases were 19.5 +/- 15.6% (percentage of tumor cells stained) by Ki-67 (range, 1-86%) and 15.7 +/- 9.6% (S + G2M) by flow cytometry (range, 3-60%), which correlated significantly at r = 0.53 and P = 0.005. The correlation was less strong in tumors with low S-phase values (less than or equal to 10%, r = 0.28) than in tumors with intermediate and high S-phase values (r = 0.66). Ki-67 staining percentages did not correlate with patient age, sex, or tissue origin of the tumor. Ki-67 staining appears comparable to flow cytometry determination of TPF in solid malignancies with intermediate and high S-phase values. In tumors with low S-phase values, Ki-67 immunostaining shows higher TPF values, which perhaps reflect an increase in the proportion of G1-phase cells or dilutional effect of nonneoplastic cells in the tumors with low proliferative fraction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Division*
  • Chi-Square Distribution
  • DNA Replication
  • DNA, Neoplasm / analysis
  • Female
  • Flow Cytometry
  • G2 Phase
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen
  • Male
  • Middle Aged
  • Mitotic Index
  • Neoplasms / pathology*
  • Nuclear Proteins / analysis*
  • S Phase
  • Staining and Labeling


  • DNA, Neoplasm
  • Ki-67 Antigen
  • Nuclear Proteins