Selective proliferation during the preneoplastic state: an example in liver

The development of malignancy in several tissues appears to result from a multistep process involving focal populations of phenotypically altered cells. These altered populations do not have malignant properties initially but apparently have an enhanced potential for malignant evolution following perturbations which result in their selective growth. In liver, for example, a 'selection pressure' adequate for preferential growth of carcinogen-altered hepatocytes may result when a cytotoxic environment, inhibitory for normal hepatocyte proliferation, is coupled with a stimulus for proliferation of the altered hepatocytes. The application of an appropriate selection pressure results in selective proliferation of these putative premalignant hepatocyte populations and a high incidence of liver cancer. In the absence of an adequate selection pressure, the altered hepatocytes fail with no evidence for their recognition and eradication of the host. Conditions for selective proliferation of premalignant populations may be an essential component of malignant evolution in liver and in other extrahepatic sites.