These observations raised the hypothesis that the well reported loss of TP53 in most of human carcinomas could be preceded by TP53 loss in stromal cells which, in turn, would happen as a consequence of an initial driver genetic event in epithelial tissue, such as Rb gene loss, responsible for not only promoting a permissive microenvironment propitious to initiated cells, but also for contributing to an important event in tumor progression which is TP53 loss. This evidence concerns the gene RB1 and neoplasm.