AMPLIFICATION OF C-MYC BUT NOT OF C-ERBB-2 IS ASSOCIATED WITH HIGH PROLIFERATIVE CAPACITY IN BREAST-CANCER

Proliferative capacity provides an independent prognostic marker of pr ogression in breast cancer. Little is known about the molecular mechan isms influencing the cell division rate in mammary carcinomas. In orde r to address this issue, the copy numbers of c-erbB-2 (HER/neu) and c- myc protooncogenes that have been shown to be amplified in aggressive types of cancers were determined in 60 mammary carcinomas and related to the proliferation rate. The proliferative activity was determined b y labeling of the proliferation-associated nuclear antigen which is de fined by the recently described monoclonal antibody Ki-S1. Approximate ly one-third of samples under investigation displayed a Ki-S1 labeling index exceeding 30%. In this subgroup, amplification of c-myc was fou nd in 52.6%, whereas in the remaining cases, 26.1 % exhibited an enhan ced copy number of c-myc (P < 0.025). By contrast. c-erbB-2 amplificat ion was not found to be associated with a higher proliferation index. Except for one case of invasive lobular carcinoma, both protooncogenes exhibited regular copy numbers in the low proliferation subgroup (<20 %; P < 0.03). We conclude from our findings that c-myc amplification m ay be one of the molecular causes underlying the highly proliferating phenotype of mammary carcinoma, known to be associated with an unfavor able clinical course.