Moreover, our group has analyzed the predictive value of topo II a in a population of node-positive breast cancer patients randomly treated either with anthracyclines or with CMF (Belgian cooperative trial). In a first study, topo II a was evaluated by immunohistochemistry, which allows the detection of topo II a protein expression. The results of this study suggested that patients deriving the highest benefit from anthracyclines were those in which topo II a protein is immunostained in more than 10% of tumor cells. The main findings of this study should be seen as hypothesis-generating because of the limited number of patients evaluated (about fifty in each study arm) and because topo II a protein levels depend on gene amplification as well as on tumor proliferation rate. Therefore, topo II a protein expression does not necessarily reflect topo II a gene status.