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 |
| Â | Â | 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 |
| Â | Â | Reproducible | Requires time-consuming autoradiography Needs fresh tissue |
| Â | Flow cytometry | Can use on wide variety of tissue preparations | Requires a relatively large tumour sample |
| Â | Â | Quick way of analysing many cells | Poor reproducibility due to variability in tissue preparation and analysis between laboratories |
| Â | BrdU monoclonal antibodies/immunohistochemistry | Better resolution and reproducibility than tritiated thymidine labeling | Requires fresh tissue and careful preparation |
| Â | Â | 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 |
| Â | Â | Sensitive | Variability in fixation can affect staining |
| Â | Â | Newer antibodies can be used on archival tissue | Â |
| Â | PCNA monoclonal antibody staining | Only need a small amount of tissue | Poor correlations with other methods, prognostic factors and clinical outcome |
| Â | Â | Sensitive | Scoring can be time consuming |
| Â | Â | Â | 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 |
| Â | Â | Can be performed on small, archival tissue samples | Â |
| Â | Â | Not influenced by stromal proliferation | Â |
PET | Radiolabelled fluorothymidine incorporation detected by PET scans | Non-invasive | Patient exposure to radiation |
| Â | Â | Enables monitoring of proliferative changes during treatment | Yet to be verified as an accurate measure of proliferation |
| Â | Â | Gives a global image of tumour, avoiding sampling errors due to heterogeneity | Expensive and supply of radio-tracer is limited |