Assessment of cellular proliferation by calculation of mitotic index and by immunohistochemistry

The ability of most carcinomas to metastasize to different organs, where they grow and gradually destroy the surrounding tissues, is the feature of this disease that both increases morbidity and significantly reduces a patient's survival time. One of the ways of contributing to the prediction of the likely course of a malignancy is by measuring the proliferative activity of the primary tumor. This allows treatment to be tailored according to the predicted aggressiveness of the disease (extrapolated from the likely growth rate). A crude estimate of a tumor's proliferation rate is to measure the change in clinical size over a period of time. However, this is not particularly accurate, as, first, clinical size and pathological tumor size are often different, and second, an increase in clinical size could be due to either increased cell size (hypertrophy) or increased cell number (hyperplasia) or even a variation in non-neoplastic elements such as fibrotic tissue. For many years microscopists used the number of mitotic figures present in a tissue section to estimate how rapidly the cells are proliferating and thereby gauge how aggressive the tumor was likely to be. With a few refinements, mainly associated with the method of evaluation, this technique continues to be used to measure the proliferative activity of tumors today (1). For some tumors, mitotic activity is used in conjunction with other histological or clinical parameters to "grade" or "index" a tumor, as described in Chapter 1 by Roskell and Buley, and this information is used to determine the most appropriate way of treating the patient (2-5).