Ki-S1, a novel proliferative marker: flow cytometric assessment of staining in human breast carcinoma cells

Br J Cancer. 1993 Apr;67(4):657-62. doi: 10.1038/bjc.1993.122.

Abstract

There is considerable interest in immunohistochemical markers of proliferation which are suitable for use on routinely fixed clinical material. The novel proliferation-associated antibody Ki-S1 shows promise in this respect. In this study we have: (i) defined the pattern of Ki-S1 labelling relative to the cell cycle phase; (ii) investigated the labelling pattern with Ki-S1 on a human breast cell line (ZR75) under varying proliferative conditions induced by serum deprivation and refeeding; (iii) examined in a flow cytometric study Ki-S1 staining in archival, clinical breast carcinoma samples. In exponentially growing cells Ki-S1 showed a marked cell cycle phase-specific variation in staining intensity which increased linearly through the S-phase, was high in G2 and reached its peak in mitosis. Ki-S1 staining intensity mirrored the changes in proliferative activity of ZR75 cells during serum deprivation and refeeding. In a small series of human breast carcinoma, Ki-S1 staining intensity correlated with S-phase fraction (SPF) derived from DNA profiles. The antigen labelled by Ki-S1 is extremely robust, resisting degradation by fixation and by an aggressive enzymic tissue disaggregation method. Ki-S1 warrants further investigation as a proliferation-related marker, particularly for routine clinical application.

MeSH terms

  • Animals
  • Antibodies, Neoplasm / analysis*
  • Antigens, Neoplasm / analysis*
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Cell Division / physiology
  • Cell Nucleus / chemistry
  • DNA Topoisomerases, Type II
  • DNA, Neoplasm / analysis
  • DNA-Binding Proteins
  • Flow Cytometry
  • Humans
  • Metaphase / physiology
  • Mice
  • Mice, Inbred BALB C
  • Nuclear Proteins / analysis*
  • Paraffin Embedding
  • S Phase / physiology
  • Staining and Labeling / methods
  • Tumor Cells, Cultured

Substances

  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Nuclear Proteins
  • DNA Topoisomerases, Type II