Affiliations: Division of Cellular and Molecular Analysis, Department of Oncology–Pathology, Karolinska Institute, Cancer Center Karolinska, R8:04, SE‐171 76, Stockholm, Sweden | Genetics Department, Division of Clinical Sciences, National Cancer Institute, NIH, Building 9, Room 1N105, 9 Memorial Drive, Bethesda, MD 20892, USA
Note: [] Corresponding author: Thomas Ried, MD, Genetics Department, Division of Clinical Sciences, National Cancer Institute, NIH, Bldg. 9, Rm. 1N105, 9 Memorial Drive, Bethesda, MD 20892, USA. Tel.: +1 301 594 3118; Fax: +1 301 435 4428; E‐mail: riedt@mail.nih.gov.
Abstract: In order to evaluate biological and genetic properties of early breast carcinomas we analyzed microdissected tissue from 33 primary breast carcinomas stage T1b and T1c with respect to the nuclear DNA content, the expression pattern of Ki‐67, cyclin A, p27KIP1, p53 and p21WAF1, and chromosomal gains and losses. The results show that T1b carcinomas (6–10 mm, n=17) were frequently near‐diploid (53%) with low proliferative activity and staining patterns of p53 and p21WAF1 that suggest the presence of wild type protein. The majority (12/16) of the T1c tumors (11–20 mm), however, was aneuploid, and proliferative activity and p53 expression were increased. Larger tumor size correlated with an increasing number of chromosomal copy number changes and in particular with regional amplifications. High level copy number increases (amplifications), however, were found exclusively in the aneuploid tumors. Amplification events correlated with elevated cyclin A and reduced p27 expression, respectively. Our results suggest that the sequential acquisition of genomic imbalances during tumor progression is accelerated in aneuploid tumors, and may contribute to the increased malignancy potential.
