Kleinschmidt-DeMasters B K, Heinz David, McCarthy Paul J, Bobak Joanna B, Lillehei Kevin O, Shroyer A Laurie W, Shroyer Kenneth R
Department of Pathology, University of Colorado Health Sciences Center, Denver, USA.
Arch Pathol Lab Med. 2003 Jul;127(7):826-33. doi: 10.5858/2003-127-826-SIG.
Survivin is a novel inhibitor of apoptosis that acts via a pathway independent of bcl-2. Little is known about its distribution in brain tumors or how it correlates with other biomarkers of malignancy, such as telomerase, an enzyme that plays a critical role in cellular immortalization and cancer biology.
To assess survivin protein expression in gliomas and to compare expression with that of telomerase.
Immunohistochemical staining for survivin protein expression was performed using an antibody developed in our laboratory. Quantitative survivin messenger RNA (mRNA) levels were assessed by reverse transcriptase-polymerase chain reaction. In selected cases, survivin results were compared with quantitative telomerase values analyzed by polymerase chain reaction-based telomerase repeat amplification protocol (TRAP) assay. Twenty-five tumor tissue samples from 16 cases of glioblastoma multiforme (GBM; including multiple tissue samples in 6 patients), 2 grade II gliomas, 4 grade III gliomas, and 3 control temporal lobectomy specimens were studied.
Nuclear immunoreactivity for survivin protein and survivin mRNA were detectable in most glioma samples, regardless of grade. Glioblastoma multiforme demonstrated moderate protein expression and survivin mRNA levels compared to epithelial malignancies previously tested in our laboratory. Although the association of survivin mRNA with the levels of telomerase within the GBM cases did not reach statistical significance, most GBMs also expressed survivin. The quantitative score for survivin mRNA was higher in GBMs than in grade II and III gliomas (P =.02), after accounting for multiple specimens per patient.
Quantitative survivin mRNA analysis, but not immunohistochemistry, distinguished GBMs from lower grade gliomas. Mechanisms that promote both cell proliferation (telomerase expression) and cell survival (survivin expression) are often activated in GBMs.
生存素是一种新型凋亡抑制因子，通过独立于bcl-2的途径发挥作用。关于其在脑肿瘤中的分布或与其他恶性生物标志物（如端粒酶，一种在细胞永生化和癌症生物学中起关键作用的酶）的相关性知之甚少。
评估生存素蛋白在胶质瘤中的表达，并与端粒酶的表达进行比较。
使用我们实验室研发的抗体进行生存素蛋白表达的免疫组织化学染色。通过逆转录-聚合酶链反应评估生存素信使核糖核酸（mRNA）的定量水平。在选定病例中，将生存素检测结果与通过基于聚合酶链反应的端粒酶重复扩增方案（TRAP）分析的定量端粒酶值进行比较。研究了来自16例多形性胶质母细胞瘤（GBM；包括6例患者的多个组织样本）、2例II级胶质瘤、4例III级胶质瘤和3例对照颞叶切除标本的25个肿瘤组织样本。
无论级别如何，在大多数胶质瘤样本中均可检测到生存素蛋白和生存素mRNA的核免疫反应性。与我们实验室之前检测的上皮性恶性肿瘤相比，多形性胶质母细胞瘤表现出中度蛋白表达和生存素mRNA水平。尽管GBM病例中生存素mRNA与端粒酶水平的相关性未达到统计学意义，但大多数GBM也表达生存素。在考虑到每位患者的多个标本后，GBM中生存素mRNA的定量评分高于II级和III级胶质瘤（P = 0.02）。
定量生存素mRNA分析而非免疫组织化学可区分GBM与低级别胶质瘤。促进细胞增殖（端粒酶表达）和细胞存活（生存素表达）的机制在GBM中通常被激活。
