Taback B, Giuliano A E, Hansen N M, Hoon D S
Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California 90404, USA.
Ann N Y Acad Sci. 2001 Sep;945:22-30. doi: 10.1111/j.1749-6632.2001.tb03860.x.
Breast cancer is the most common malignancy affecting women. Advances in screening have resulted in an increasing trend towards detecting earlier stage tumors associated with a longer disease-free survival. Because of this prolonged latency period, it is critical to identify patients early in their disease course who are at increased risk for recurrence, whereby treatment decisions may be altered accordingly based on more precise information. Molecular markers that demonstrate prognostic importance as well as utility for assessing subclinical disease progression offer one such approach. Specifically, circulating microsatellite alterations that reflect those genetic events occurring in tumors and that can be serially assessed through a minimally invasive procedure are a logistically practical method. In this study, serum was collected preoperatively from 56 patients with early stage breast cancer (AJCC stages I/II) and assessed for loss of heterozygosity (LOH) using 8 microsatellite markers. Twelve (21%) of 56 patients demonstrated LOH in their serum for at least one marker. Histopathologic correlation revealed an association between the presence of circulating LOH in serum and those tumors with increased proliferation indices as characterized by an increased diploid index, elevated MIB-1 fraction, and abnormal ploidy. These findings demonstrate the presence of circulating microsatellite alterations in the serum from patients with early stage breast cancer. The association of known poor prognostic features found in tumors with increased nuclear activity not only suggests a possible etiology for their presence, but also offers a potential blood-based surrogate marker for this disease that may demonstrate clinical utility in long-term follow-up studies.
乳腺癌是影响女性的最常见恶性肿瘤。筛查技术的进步导致检测早期肿瘤的趋势增加，这些早期肿瘤与更长的无病生存期相关。由于这种较长的潜伏期，在疾病进程早期识别复发风险增加的患者至关重要，据此可根据更精确的信息相应地改变治疗决策。显示出预后重要性以及评估亚临床疾病进展效用的分子标志物提供了一种这样的方法。具体而言，反映肿瘤中发生的那些基因事件且可通过微创程序进行连续评估的循环微卫星改变是一种符合逻辑的实用方法。在本研究中，术前从56例早期乳腺癌（美国癌症联合委员会分期I/II期）患者中采集血清，并使用8个微卫星标志物评估杂合性缺失（LOH）。56例患者中有12例（21%）血清中至少有一个标志物显示出LOH。组织病理学相关性显示，血清中循环LOH的存在与那些具有增殖指数增加特征的肿瘤之间存在关联，这些肿瘤的特征为二倍体指数增加、MIB-1分数升高和倍体异常。这些发现证明了早期乳腺癌患者血清中存在循环微卫星改变。在肿瘤中发现的已知不良预后特征与核活性增加相关，这不仅提示了它们存在的可能病因，还为这种疾病提供了一种潜在的基于血液的替代标志物，可能在长期随访研究中显示出临床效用。
