QUANTITATIVE MICROSCOPY AND TUMOR-CELL PROLIFERATION

The number of cell probes is rapidly increasing. During the last few y ears it has become possible to label total nuclear DNA (Feulgen), synt hesized DNA (BrdU), specific A/T versus G/C rich DNA, cell cycle prote ins (PCNA, Ki67), hormonal receptors (ER, PR, EGF), cde genes and gene primary transcripts, etc. Taking advantage of this roster of cellular probes to assess cell kinetics in normal and malignant tissues implie s 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 qu antitative results are properly interpreted. Confusions are often made between the respective meaning of i) reduced cell cycle speed (cell c ycle duration), ii) increased proportion of proliferative cells (growt h fraction), and iii) fraction of cells in S phase (SPF) and mitotic i ndex (proportion of mitoses) which all tune the cell proliferative act ivity. The contribution of these biological cell population features t o tumour growth is illustrated. Examples based on image cytometry are presented to define the individual tumour cell proliferation profile a nd tumour heterogeneity for proliferation profiles. It will be finely demonstrated how quantitative microscopy can turn the 'conventional st atic histological picture' of a tumour into a 'functional picture' tha t might support decision for therapeutic strategies.