[Proliferative activity and defective replication in breast cancer].

The highly proliferating phenotype of mammary carcinoma is known to be associated with a particularly aggressive clinical course. We have been interested in the underlying molecular causes that give rise to the increased proliferative activity Proliferative activity was determined immunohistochemically by the detection of topoisomerase II-alpha (Ki-S1). The subgroup of highly proliferating tumors with a Ki-S1 index exceeding 30% was characterized by a high frequency of c-myc amplification and aberrant p53 expression, whereas tumors, with a low mitotic activity rarely exhibited gene amplification or an altered p53 expression. We conclude, that the highly proliferating phenotype is not capable of regular replication and tends to develop gene amplifications. One of the causes might be a defective cell cycle control by p53.