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Table 1 Methods of measuring proliferation

From: Measuring proliferation in breast cancer: practicalities and applications

Method Description Advantages Limitations
Mitotic index Number of mitotic bodies on light microscopy Cheap and simple staining method Variability in counting
   Can be used on paraffin-embedded specimens Appearance of apoptosis/nuclear pyknosis can be confused with mitosis
Relationship with proliferative rate might not be linear
S-phase fraction Thymidine labelling index Accurate even in slowly proliferating tumours Requires handling of radioisotope
   Reproducible Requires time-consuming autoradiography Needs fresh tissue
  Flow cytometry Can use on wide variety of tissue preparations Requires a relatively large tumour sample
   Quick way of analysing many cells Poor reproducibility due to variability in tissue preparation and analysis between laboratories
  BrdU monoclonal antibodies/immunohistochemistry Better resolution and reproducibility than tritiated thymidine labeling Requires fresh tissue and careful preparation
   No need for autoradiography Scoring can be time consuming
Nuclear antigen immunohistochemistry Ki67/MIB-1 monoclonal antibody staining Only need a small amount of tissue Scoring can be time consuming
   Sensitive Variability in fixation can affect staining
   Newer antibodies can be used on archival tissue  
  PCNA monoclonal antibody staining Only need a small amount of tissue Poor correlations with other methods, prognostic factors and clinical outcome
   Sensitive Scoring can be time consuming
    Variability in fixation can affect staining
Cyclins Proteins that vary in expression during the cell Cycle Different cyclins associated with different cell cycle phases so can target cells committed to proliferation Relatively new technique – not widely available for routine use
   Can be performed on small, archival tissue samples  
   Not influenced by stromal proliferation  
PET Radiolabelled fluorothymidine incorporation detected by PET scans Non-invasive Patient exposure to radiation
   Enables monitoring of proliferative changes during treatment Yet to be verified as an accurate measure of proliferation
   Gives a global image of tumour, avoiding sampling errors due to heterogeneity Expensive and supply of radio-tracer is limited
  1. BrdU, 5-bromodeoxyuridine; PCNA, proliferating cell nuclear antigen; PET, positron emission tomography.