Survivin gene expression in early-stage non-small cell lung cancer
Survivin gene expression in early-stage non-small cell lung cancer
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DOI：
10.1002/path.1388
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发表时间：
2003-08-01
影响因子：
7.3
通讯作者：
Bosari, S
中科院分区：
文献类型：
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作者：
Falleni, M;Pellegrini, C;Bosari, S
生存素是一种凋亡抑制蛋白，在大多数人类恶性肿瘤中过表达，并参与有丝分裂调节和细胞活力的保持。为探讨生存素在早期非小细胞肺癌（NSCLC）中的表达及其临床意义，采用实时荧光定量RT-PCR和免疫组化方法分别检测83例I期（IA和IB）手术切除的NSCLC中生存素mRNA和蛋白的表达。在所有非肿瘤性肺组织样本和分析的肿瘤中均可检测到生存素mRNA水平。80例肺癌（96%）Survivin mRNA表达高于正常肺组织（P = 0.008）。在所有肿瘤中，生存素转录本在鳞状细胞癌中以较高的水平存在（p = 0.0022）。70%和80%的肿瘤细胞质和核免疫反应，分别发现，两者都存在于54%。细胞质免疫反应性与肿瘤分期相关（p = 0.019）。Survivin表达水平与患者生存率无关。在一个标本中，在发育不良的支气管鳞状化生中观察到细胞质和局灶性核免疫染色。这些结果表明，生存素过表达几乎总是存在于早期NSCLC，这表明这种蛋白质可能在肺肿瘤发生中发挥作用。这种普遍存在的表达使生存素成为肺癌新疗法的一个有吸引力的新靶点。此外，本研究还证明了生存素过表达可用于诊断目的，定量实时RT-PCR可作为评估NSCLC中生存素活化的有用工具。版权所有（C）2003约翰威利父子有限公司。
Survivin is an inhibitor of apoptosis protein, overexpressed in most human malignancies and implicated in mitosis regulation and preservation of cell viability. In order to investigate the prevalence and clinical significance of survivin in early-stage non-small cell lung carcinoma (NSCLC), survivin mRNA levels and protein expression were evaluated, using quantitative real-time RT-PCR and immunohistochemistry, respectively, in a series of 83 patients with stage I (IA and IB) surgically resected NSCLC. Detectable survivin mRNA levels could be demonstrated in all non-neoplastic lung tissue samples and in the tumours analysed. Survivin mRNA levels were elevated in 80 carcinomas (96%) compared to normal lung (P = 0.008). Among all tumours, survivin transcripts were present at a higher level in squamous cell carcinomas (p = 0.0022). Cytoplasmic and nuclear immunoreactivity was found in 70% and 80% of tumours, respectively and both were present in 54%. Cytoplasmic immunoreactivity correlated with tumour stage (p = 0.019). Survivin expression levels did not correlate with patient survival. In one specimen, cytoplasmic and focal nuclear immunostaining was observed in dysplastic bronchial squamous metaplasia. These results document that survivin overexpression is almost always present in early-stage NSCLC, suggesting that this protein may play a role in lung tumourigenesis. This ubiquitous expression makes survivin an appealing new target for novel therapies in lung cancer. In addition, this study also documents that survivin overexpression could be exploited for diagnostic purposes and that quantitative real-time RT-PCR can be a useful tool for evaluating survivin activation in NSCLC. Copyright (C) 2003 John Wiley Sons, Ltd.