Quantitative microscopy and tumour cell proliferation

The number of cell probes is rapidly increasing. During the last few years it has become possible to label total nuclear DNA (Feulgen), synthesized DNA (BrdU), specific A/T versus G/C rich DNA, cell cycle proteins (PCNA, Ki67), hormonal receptors (ER, PR, EGF), cdc genes and gene primary transcripts, etc. Taking advantage of this roster of cellular probes to assess cell kinetics in normal and malignant tissues implies not only quantitating their amount per cell but also analysing their intra-cellular respective distribution and inter-cellular variation. Image cytometry is the tool of choice for this purpose provided the quantitative results are properly interpreted. Confusions are often made between the respective meaning of i) reduced cell cycle speed (cell cycle duration), ii) increased proportion of proliferative cells (growth fraction), and iii) fraction of cells in S phase (SPF) and mitotic index (proportion of mitoses) which all tune the cell proliferative activity. The contribution of these biological cell population features to tumour growth is illustrated. Examples based on image cytometry are presented to define the individual tumour cell proliferation profile and tumour heterogeneity for proliferation profiles. It will be finely demonstrated how quantitative microscopy can turn the 'conventional static histological picture' of a tumour into a 'functional picture' that might support decision for therapeutic strategies.