Telomerase activity in human breast tumors
Telomerase activity in human breast tumors
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DOI：
10.1093/jnci/88.2.116
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发表时间：
1996-01-17
期刊：
影响因子：
--
通讯作者：
Shay, JW
中科院分区：
文献类型：
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作者：
Hiyama, E;Gollahon, L;Shay, JW
背景：正常体细胞中未检测到核糖核蛋白酶端粒酶的活性；因此，随着每次细胞分裂，由端粒重复序列TTAGGG组成的染色体末端逐渐被侵蚀。目前获得支持的模型是端粒酶活性在生殖系和永生细胞中维持端粒长度，从而补偿“末端复制问题”。“目的：我们的目标是确定端粒酶活性在恶性乳腺癌进展过程中何时被重新激活，以及端粒酶活性的知识是否可能成为乳腺癌诊断和潜在治疗的指标。”方法：采用聚合酶链反应为基础的端粒酶活性测定方法，对140例乳腺癌标本（140例）、4例叶状肿瘤（4例）、38例非癌性病变(20例纤维腺瘤、17例纤维囊性疾病、1例男性乳房发育症（38例）和55例邻近非癌性乳腺组织（140例乳腺癌患者中的55例）的端粒酶活性进行了检测，并对33例细针抽吸乳腺标本（33例）进行了分析。结果：在手术切除的样本中，130例乳腺癌中有130例（93%）检测到端粒酶活性，68%的I期原发性乳腺癌、73%的小于20 mm的癌症和81%的腋窝淋巴结阴性癌症检测到端粒酶活性，此外，超过95%的晚期肿瘤检测到端粒酶活性，但55例邻近非癌组织中只有2例（4%）检测到端粒酶活性。虽然在17例纤维囊性疾病标本中未检测到端粒酶活性，但在20例纤维腺瘤中有9例（45%）检测到端粒酶活性低得惊人。在细针抽吸获得的样本中，14例细针抽吸样本含有端粒酶活性并随后接受手术的患者中有14例（100%）被确诊患有乳腺癌。对125例有手术年龄、疾病分期、肿瘤大小、淋巴结状态、肿瘤组织学和绝经期数据的患者标本进行多因素分析表明，分期与端粒酶活性的相关性最强（I期与II-IV期：比值比= 1.0 vs 73.4； 95%可信区间= 2.0-959.0;P = 0.02）。结论：在超过95%的晚期乳腺癌中检测到端粒酶活性，而在19%-32%的较不晚期乳腺癌中检测不到端粒酶活性。由于目前无法确定端粒酶活性与患者生存之间的任何关联，端粒酶活性缺乏是否预示着有利的结果仍有待确定。
Background: The activity of the ribonucleoprotein enzyme telomerase is not detected in normal somatic cells; thus, with each cell division, the ends of chromosomes consisting of the telomeric repeats TTAGGG progressively erode. The current model gaining support is that telomerase activity in germline and immortal cells maintains telomere length and thus compensates for the ''end-replication problem.'' Purpose: Our objective was to determine when telomerase activity is reactivated in the progression to malignant breast cancer and if knowledge of telomerase activity may be an indicator for the diagnosis and potential treatment of breast cancer. Methods: Using a polymerase chain reaction-based telomerase activity assay, we examined telomerase activity in 140 breast cancer specimens (from 140 patients), four phyllodes tumors (from four patients), 38 noncancerous lesions (20 fibroadenomas, 17 fibrocystic diseases, one gynecomastia; from 38 patients), and 55 adjacent noncancerous mammary tissues (from 55 of the 140 breast cancer patients), In addition, 33 fine-needle-aspirated breast samples (from 33 patients) were analyzed. Results: Among surgically resected samples, telomerase activity was detected in 130 (93%) of 130 breast cancers, Telomerase activity was detected in 68% of stage I primary breast cancers, in 73% of cancers smaller than 20 mm, and in 81% of axillary lymph node-negative cancers, Moreover, the activity was detected in more than 95% of advanced stage tumors but in only two (4%) of 55 adjacent noncancerous tissues. While telomerase activity was not detected in any of 17 specimens of fibrocystic disease, surprisingly low levels of telomerase activity were detected in nine (45%) of 20 fibroadenomas. Among samples obtained by fine-needle aspiration, 14 (100%) of 14 patients whose fine-needle-aspirated specimen contained telomerase activity and who subsequently underwent surgery were confirmed to have breast cancer. Multivariate analysis of 125 specimens from patients for whom data were available on age at surgery, stage of disease, tumor size, lymph node status tumor histology, and menopausal status indicated that stage classification exhibited the strongest association with telomerase activity (for stage I versus stages II-IV: odds ratio = 1.0 versus 73.4; 95% confidence interval = 2.0-959.0; P = .02). Conclusion: Telomerase activity was detected in more than 95% of advanced stage breast cancers, It was absent in 19%-32% of less advanced cancers, Since a determination of any association between telomerase activity and patient survival is not possible at the present time, it remains to be determined whether lack of telomerase activity predicts for favorable outcome.