Fordyce Colleen A, Heaphy Christopher M, Bisoffi Marco, Wyaco Jessica L, Joste Nancy E, Mangalik Aroop, Baumgartner Kathy B, Baumgartner Richard N, Hunt William C, Griffith Jeffrey K
Department of Biochemistry and Molecular Biology, 1 University of New Mexico, Albuquerque, NM 87131-0001, USA.
Breast Cancer Res Treat. 2006 Sep;99(2):193-202. doi: 10.1007/s10549-006-9204-1. Epub 2006 Jun 3.
To evaluate the hypothesis that telomere DNA content (TC) in breast tumor tissue correlates with TNM staging and prognosis.
Slot blot assay was used to quantitate TC in 70 disease-free normal tissues from multiple organ sites, and two independent sets of breast tumors containing a total of 140 samples. Non-parametric Rank-Sums tests, logistic regression and Cox proportional hazards models were used to evaluate the relationships between TC and tumor size, nodal involvement, TNM stage, 5-year survival and disease-free interval.
TC in 95% of normal tissues was 75-143% of that in the placental DNA standard, whereas only 50% of tumors had TC values in this range. TC was associated with tumor size (p=0.02), nodal involvement (p<0.0001), TNM stage (p=0.004), 5-year overall survival (p=0.0001) and 5-year disease-free survival (p=0.0004). A multivariable Cox model was developed using age at diagnosis, TNM stage and TC as independent predictors of breast cancer-free survival. Relative to the high TC group (>123% of standard), low TC (<101% of standard) conferred an adjusted relative hazard of 4.43 (95% CI 1.4-13.6, p=0.009). Receiver operating characteristic curves using thresholds defined by the TC distribution in normal tissues predicted 5-year breast cancer-free survival with 50% sensitivity and 95% specificity, and predicted death due to breast cancer with 75% sensitivity and 70% specificity.
TC in breast cancer tissue is an independent predictor of clinical outcome and survival interval, and may discriminate by stage.
评估乳腺癌组织中端粒DNA含量（TC）与TNM分期及预后相关的假说。
采用狭缝印迹法对来自多个器官部位的70份无病正常组织以及两组独立的共140份乳腺癌样本中的TC进行定量分析。使用非参数秩和检验、逻辑回归和Cox比例风险模型评估TC与肿瘤大小、淋巴结受累情况、TNM分期、5年生存率和无病生存期之间的关系。
95%的正常组织中TC为胎盘DNA标准的75% - 143%，而只有50%的肿瘤TC值在此范围内。TC与肿瘤大小（p = 0.02）、淋巴结受累情况（p < 0.0001）、TNM分期（p = 0.004）、5年总生存率（p = 0.0001）和5年无病生存率（p = 0.0004）相关。构建了一个多变量Cox模型，将诊断时年龄、TNM分期和TC作为无乳腺癌生存期的独立预测因素。相对于高TC组（>标准的123%），低TC组（<标准的101%）的调整后相对风险为4.43（95%CI 1.4 - 13.6，p = 0.009）。使用正常组织中TC分布定义的阈值绘制的受试者工作特征曲线预测5年无乳腺癌生存期的灵敏度为50%，特异性为95%，预测因乳腺癌死亡的灵敏度为75%，特异性为70%。
乳腺癌组织中的TC是临床结局和生存间隔的独立预测因素，并可能按分期进行区分。
