Assessing cellular proliferation: what's worth measuring?

The assessment of cellular proliferation is, in the main, carried out on histological material. Ideally, such methods should be applicable to routinely processed tissues, they should be relatively inexpensive and the results easily quantified and interpreted. A knowledge of what is 'normal' within the tissue from both a temporal and spatial point of view is essential. There is a burgeoning literature on novel markers of cell proliferation, usually these are immunohistochemically based, each method with its own unique set of conditions for optimal tissue processing. Some would argue this is simply a process of 'reinventing the wheel' since mitotic counting is a perfectly adequate indicator of proliferation, but we could justly counter that a labelling index (S-phase or growth fraction) is more likely to produce an accurate assessment when the sample size is small. In tumours, tissue heterogeneity is likely to render any single measurement meaningless. To date, there are no reliable validated immunohistochemical markers of the labelling index in animal tissues which visualise naturally occurring proliferation-associated molecules, though this may change shortly.