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端粒酶活性及端粒长度改变在颅内脑膜瘤组织学特征中的意义

Implication of telomerase activity and alternations of telomere length in the histologic characteristics of intracranial meningiomas.

作者信息

Chen H J, Liang C L, Lu K, Lin J W, Cho C L

机构信息

Division of Neurosurgery, Chang Gung University and Medical Center at Kaohsiung, Kaohsiung Hsien, Taiwan.

出版信息

Cancer. 2000 Nov 15;89(10):2092-8. doi: 10.1002/1097-0142(20001115)89:10<2092::aid-cncr9>3.0.co;2-n.

Abstract

BACKGROUND

Telomerase activity and telomere length have been shown to be involved in the control of cell proliferation and regulation of cell senescence. The expression of telomerase activity may endow cells with the capacity of unlimited proliferation and immortality. The authors examined the telomerase activity and telomere length of intracranial meningiomas to determine the relation between the results and the clinicopathologic behavior of these tumors.

METHODS

Sixty-two specimens of meningiomas including 13 atypical and malignant tumors were used in this study. Telomerase activity was measured with polymerase chain reaction and enzyme-linked immunosolvent assay. Telomere length was measured by detecting the terminal restriction fragments using Southern blots.

RESULTS

Detectable telomerase activity was found in 4 of 13 (30.8%) malignant or atypical meningiomas and only 1 in 49 benign meningiomas (P = 0.006). Elongated telomere length was measured in 6 of 13 (46.1%) patients with malignant or atypical meningiomas and only 1 of 48 (2.1%) in those with benign tumors (P = 0.0002). Three of 4 (75%) of malignant or atypical meningiomas with detectable telomerase activity revealed shortened telomere length, and all tumors with elongated telomere length displayed undetectable telomerase activity. The percentage of malignant or atypical meningiomas with detectable telomerase activity or elongated telomere were significantly higher (76.9%) than that of benign tumors (4.0%). The proliferative index was calculated as the percentage of tumor cell nuclei immunoreactive for Ki-67 to total tumor nuclei. The mean values of proliferative index in benign, atypical, and malignant meningiomas were 1.2, 11.0, and 30.0, respectively.

CONCLUSIONS

The results indicate that telomerase activation may be a critical step in the pathogenesis of malignant or atypical meningioma. Elongation of the telomere length also implicates the high potential for malignant behavior in these tumors.

摘要

背景

端粒酶活性和端粒长度已被证明参与细胞增殖的控制和细胞衰老的调节。端粒酶活性的表达可能赋予细胞无限增殖和永生的能力。作者检测了颅内脑膜瘤的端粒酶活性和端粒长度,以确定这些结果与这些肿瘤临床病理行为之间的关系。

方法

本研究使用了62例脑膜瘤标本,其中包括13例非典型和恶性肿瘤。采用聚合酶链反应和酶联免疫吸附测定法测量端粒酶活性。通过Southern印迹检测末端限制片段来测量端粒长度。

结果

在13例恶性或非典型脑膜瘤中有4例(30.8%)检测到端粒酶活性,而在49例良性脑膜瘤中仅1例(P = 0.006)。13例恶性或非典型脑膜瘤患者中有6例(46.1%)测量到端粒长度延长,而良性肿瘤患者中48例仅有1例(2.1%)(P = 0.0002)。4例检测到端粒酶活性的恶性或非典型脑膜瘤中有3例(75%)端粒长度缩短,所有端粒长度延长的肿瘤均未检测到端粒酶活性。具有可检测到端粒酶活性或端粒长度延长的恶性或非典型脑膜瘤的百分比(76.9%)显著高于良性肿瘤(4.0%)。增殖指数计算为对Ki-67免疫反应的肿瘤细胞核占总肿瘤细胞核的百分比。良性、非典型和恶性脑膜瘤的增殖指数平均值分别为1.2、11.0和30.0。

结论

结果表明端粒酶激活可能是恶性或非典型脑膜瘤发病机制中的关键步骤。端粒长度延长也意味着这些肿瘤具有较高的恶性行为潜能。

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