DNA amplifications and aneuploidy, high proliferative activity and impaired cell cycle control characterize breast carcinomas with poor prognosis
DNA amplifications and aneuploidy, high proliferative activity and impaired cell cycle control characterize breast carcinomas with poor prognosis
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DOI：
10.1155/2003/491362
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发表时间：
2003-01-01
影响因子：
3.2
通讯作者：
Ried, T
中科院分区：
文献类型：
--
作者：
Blegen, H;Will, JS;Ried, T
为了探索特定的细胞遗传学异常是否可以用于对具有明显不同临床病程的肿瘤进行分层，我们对间隔不到 2 年诊断为转移性疾病或 10 年以上未发生远处转移的患者的肿瘤进行了比较基因组杂交 (CGH)。所有患者在乳房切除术后均出现远处转移，这表明本研究中没有患者被治愈并且没有残留的肿瘤细胞。与长期幸存者相比，短期幸存者组中的肿瘤显示出更高的平均染色体拷贝改变数量。值得注意的是，短期幸存者组中亚染色体高水平拷贝数增加（扩增）的数量显着增加。在短期和长期幸存者中，反复出现的染色体增益被映射到染色体 1q、4q、8q 和 5p。短期幸存者群体中更频繁的拷贝数变化包括染色体 3q、9p、11p 和 11q 的增加以及 17p 的丢失。我们的结果表明，低度和高度恶性乳腺腺癌的特征是染色体拷贝数变化的特定模式。此外，对 Ki-67、p27(KIP1)、p21(WAF1)、p53、细胞周期蛋白 A 和细胞周期蛋白 E 表达水平的免疫组织化学评估揭示了增殖活性增加与不良预后之间的相关性。
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, p27(KIP1), p21(WAF1), p53, cyclin A and cyclin E revealed a correlation between increased proliferative activity and poor outcome.