Cell proliferation kinetics in human solid tumors: relation to probability of metastatic dissemination and long-term survival.

A large number of studies have investigated the relationship between the long-term survival and the percentage of tumor cells in S phase assessed by autoradiography after tritiated thymidine labelling, image cytometry, flow cytometry or labelling with an halogenated analog of thymidine, in various types of human solid tumors. The survey of the results clearly shows that the S-phase fraction (SPF) is of high prognostic significance in several types of cancers, in particular in breast cancers, non-Hodgkin lymphomas, ovarian cancers, neuroblastoma, bladder cancers and lung cancers. SPF was found of high independent significance in 10 of the 11 studies in which multivariate analyses of prognostic factors had been carried out. Proliferation appears generally to be of higher prognostic significance than ploidy. In view of the wide differences in the biological characteristics of the tumors studied, it is likely that the association between a high proliferation rate and the degree of tumor aggressiveness is a general feature of human solid tumors. However, high proliferative rate of tumor cells is probably not the cause of tumor biological aggressiveness but a variable associated with it. The extent to which cells escape from the regulatory systems which control their proliferation appears to be a good index of tumor progression.