Müller M, Heicappell R, Krause H, Sachsinger J, Porsche C, Miller K
Department of Urology, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany.
Eur Urol. 1999;35(3):249-55. doi: 10.1159/000019856.
An important characteristic of malignant cells is their unlimited replicative potential, their immortality. In conferring this immortality, the enzyme telomerase is believed to play a crucial role. The detection of telomerase activity provides new knowledge regarding the biologic growth behavior of tumors and offers new diagnostic and therapeutic tools.
In the present study the sensitive TRAP assay (telomeric repeat amplification protocol) was used to examine 44 malignant renal tumors and 8 benign tumors of the kidney and 52 specimens of normal renal tissue for telomerase activity.
Telomerase activity was detected in 63% of tissue samples obtained from histologically confirmed renal cell carcinomas. In cases of renal cell carcinoma restricted to the kidney, telomerase activity was detected in 58%. In cases in which tumor growth has progressed beyond the limits of the organ, telomerase activity was found in 69%. This stage dependence, however, did not reach statistical significance. No correlation to tumor grading was observed. Telomerase activity was found less frequent in chromophobe renal cell carcinomas. Neither the 8 benign renal tumors (4 oncocytomas and 4 angiomyolipomas) nor the specimens of normal kidney showed any evidence of telomerase activity.
The proportion of remarkable slow-growing renal cell carcinomas showing telomerase activity is less than in other malignancies and may correlate with biologic growth behavior. Possible explanations include the presence of an alternative pathway, called ALT (alternative lengthening of telomeres) and an association with the loss or presence of the telomerase suppressor on the short arm of chromosome 3. Prolonged follow-up will be of special interest to determine whether lack of telomerase activity predicts favorable outcome.
恶性细胞的一个重要特征是其无限的复制潜能，即永生性。人们认为，端粒酶在赋予这种永生性方面起着关键作用。端粒酶活性的检测为肿瘤的生物学生长行为提供了新的认识，并提供了新的诊断和治疗工具。
在本研究中，采用灵敏的TRAP分析法（端粒重复序列扩增法）检测44例恶性肾肿瘤、8例良性肾肿瘤以及52份正常肾组织标本中的端粒酶活性。
在经组织学确诊的肾细胞癌组织样本中，63%检测到端粒酶活性。在局限于肾脏的肾细胞癌病例中，58%检测到端粒酶活性。在肿瘤生长已超出器官界限的病例中，69%检测到端粒酶活性。然而，这种分期依赖性未达到统计学意义。未观察到与肿瘤分级的相关性。在嫌色性肾细胞癌中，端粒酶活性的发现频率较低。8例良性肾肿瘤（4例嗜酸细胞瘤和4例血管平滑肌脂肪瘤）以及正常肾脏标本均未显示任何端粒酶活性的证据。
显示端粒酶活性的生长缓慢的肾细胞癌比例低于其他恶性肿瘤，可能与生物学生长行为相关。可能的解释包括存在一种称为ALT（端粒替代延长）的替代途径，以及与3号染色体短臂上的端粒酶抑制因子的缺失或存在有关。长期随访对于确定端粒酶活性缺乏是否预示良好预后将具有特殊意义。
