AMPLIFICATION AND OVEREXPRESSION OF CYCLIN-D1 IN BREAST-CANCER DETECTED BY IMMUNOHISTOCHEMICAL STAINING

Immunohistochemical staining with a monoclonal antibody against human cyclin D1 can be used to identify breast cancers that have an amplific ation of the q13 region of chromosome II. In general, the intensity of staining is directly proportional to the degree of DNA amplification. In two unusual tumors, in which the CCND1 locus is highly amplified b ut staining is relatively weak, it appears that the DNA has undergone rearrangement and that the amplified/rearranged CCND1 allele may have reduced transcriptional activity. More significantly, the immunohistoc hemical technique identifies additional tumors in which the cyclin D1 gene is overexpressed with only marginal or undetectable increases in copy number, implying that other mechanisms can lead to deregulated ex pression. These results suggest that the frequency of overexpression i s much higher than previously concluded from DNA-based analyses and th at more than one-third of human breast cancers may contain excessive l evels of cyclin D1. The technique we describe should facilitate the de tection of this abnormality in a clinical setting and clarify its prog nostic significance.