Bednarek A K, Sahin A, Brenner A J, Johnston D A, Aldaz C M
Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas 78957, USA.
Clin Cancer Res. 1997 Jan;3(1):11-6.
Telomerase activity has been implicated to be associated with most human malignant tumors, including breast cancer. To evaluate possible associations with well-known prognostic factors in breast cancer, we performed a semi-quantitative analysis of telomerase activity levels using the very sensitive PCR-mediated telomeric repeat amplification protocol. Telomerase activity was detected in 99 of 104 breast cancer samples analyzed (95.2%), whereas no activity was detected in 10 of 10 adjacent nonmalignant breast tissues. Analysis of five breast fibroadenoma samples revealed telomerase activity in one (20%). In contrast to previous observations, we observed that 100% of stage I breast tumors were positive for telomerase activity. More interestingly, we detected telomerase activity in six of six ductal carcinoma in situ samples (i.e., stage 0). In our semiquantitative analysis of levels of enzymatic activity, we found no statistically significant correlation at the P < h 0.05 level between telomerase levels and lymph node metastasis status, estrogen and progesterone receptor status, tumor size, S-phase fraction, and ploidy. The only statistically significant correlation was found with patient age (rho = -0.3; P = 0.03). We observed no statistically significant difference in the telomerase activity levels of early tumors (stages 0 and 1) versus more advanced lesions (stages II to IV). Nevertheless, stage IV tumors displayed a tendency for higher telomerase activity levels. In summary, no clear association was observed between telomerase levels and known breast cancer prognostic indicators. However, telomerase detection by the telomeric repeat amplification protocol method, due to its high sensitivity, may be of value in early breast cancer diagnosis and detection, because our data indicate that telomerase reactivation appears to constitute a relatively early event in breast carcinogenesis.
端粒酶活性已被认为与包括乳腺癌在内的大多数人类恶性肿瘤有关。为了评估其与乳腺癌中已知预后因素的可能关联，我们使用非常灵敏的聚合酶链反应介导的端粒重复序列扩增法，对端粒酶活性水平进行了半定量分析。在分析的104个乳腺癌样本中，有99个（95.2%）检测到端粒酶活性，而在10个相邻的非恶性乳腺组织中，没有一个检测到活性。对5个乳腺纤维瘤样本的分析显示，其中1个（20%）检测到端粒酶活性。与之前的观察结果相反，我们发现I期乳腺癌肿瘤端粒酶活性阳性率为100%。更有趣的是，我们在6个原位导管癌样本（即0期）中均检测到了端粒酶活性。在我们对酶活性水平的半定量分析中，我们发现端粒酶水平与淋巴结转移状态、雌激素和孕激素受体状态、肿瘤大小、S期分数及倍体之间，在P < 0.05水平上无统计学显著相关性。唯一具有统计学显著相关性的是患者年龄（相关系数 = -0.3；P = 0.03）。我们观察到早期肿瘤（0期和I期）与更晚期病变（II至IV期）的端粒酶活性水平无统计学显著差异。然而，IV期肿瘤显示出端粒酶活性水平较高的趋势。总之，未观察到端粒酶水平与已知乳腺癌预后指标之间存在明确关联。然而，由于端粒重复序列扩增法检测端粒酶具有高灵敏度，可能在早期乳腺癌诊断和检测中具有价值，因为我们的数据表明端粒酶重新激活似乎是乳腺癌发生过程中一个相对早期的事件。
