Abstract
In order to explore whether specific cytogenetic abnormalities can be used to stratify tumors with a distinctly different clinical course, we performed comparative genomic hybridization (CGH) of tumors from patients who were diagnosed with metastatic disease after an interval of less than 2 years or who remained free from distant metastases for more than 10 years. All patients presented with distant metastases after mastectomy indicating that none of the patients in this study was cured and free of remaining tumor cells. Tumors in the group of short‐term survivors showed a higher average number of chromosomal copy alterations compared to the long‐term survivors. Of note, the number of sub‐chromosomal high‐level copy number increases (amplifications) was significantly increased in the group of short‐term survivors. In both short‐ and long‐term survivors recurrent chromosomal gains were mapped to chromosomes 1q, 4q, 8q, and 5p. Copy number changes that were more frequent in the group of short‐term survivors included gains of chromosome 3q, 9p, 11p and 11q and loss of 17p. Our results indicate that low‐ and high grade malignant breast adenocarcinomas are characterized by a specific pattern of chromosomal copy number changes. Furthermore, immunohistochemical evaluation of the expression levels of Ki‐67, p27KIP1, p21WAF1, p53, cyclin A and cyclin E revealed a correlation between increased proliferative activity and poor outcome.
Highlights
Breast cancer presents itself as a heterogeneous disease with pronounced differences in the clinical course
The integrity of the genome is maintained through the coordinated expression of genes that are involved in the control of cell cycle progression
The inactivation or functional impairment of these cell cycle regulators is a key event during carcinogenesis
Summary
Breast cancer presents itself as a heterogeneous disease with pronounced differences in the clinical course. Factors that correlate with clinical outcome include tumor stage, size and spread. These parameters rather describe the status quo of disease pro-. Previous cytogenetic and molecular analyses could correlate specific chromosomal gains or losses with tumor initiation, progression and metastatic behavior. Deletion of 1p, 7q31, 8p21–22, 16q and 17p are associated with an aggressive clinical course and a higher risk for metastatic disease [2,16,20,40,41]. Gains and amplifications of chromosome arms and bands 8q, H. Blegen et al / Predictors of survival in breast cancer
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