TTF1 expression in non-small cell lung carcinoma: association with TTF1 gene amplification and improved survival
TTF1 expression in non-small cell lung carcinoma: association with TTF1 gene amplification and improved survival
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DOI：
10.1002/path.2443
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发表时间：
2009-01-01
影响因子：
7.3
通讯作者：
Rubin, M. A.
中科院分区：
文献类型：
--
作者：
Perner, S.;Wagner, P. L.;Rubin, M. A.
获得性染色体畸变在肿瘤的发生和发展中起着重要作用。这种遗传改变发生在很大比例的非小细胞肺癌（nsclc）中，包括14q13.3的扩增，其中包含TTF1基因。我们询问TTF1扩增是否与nsclc中TTF1蛋白表达增加有关，以及TTF1是否与临床病理特征（包括患者生存）有关。我们使用FISH分析和定量免疫组织化学染色对538例瑞士非小细胞肺癌患者进行TTF1扩增和蛋白表达的调查。我们发现TTF1在13%的腺癌（ACs）和9%的鳞状细胞癌（SCCs）中扩增，并且TTF1扩增与TTF1蛋白表达增加相关。仅在ACs中，TTF1高水平表达与较小的肿瘤大小、女性性别和较长的总生存期显著相关（中位生存期82个月vs 28个月；p = 0.002）。多因素分析显示，TTF1高表达是AC患者预后良好的独立预测因子[危险比，0.56 (95% CI 0.38-0.83)；P = 0.008]。我们得出结论，TTF1扩增是nsclc亚群中TTF1高水平表达的一种机制。当高水平表达时，这种常规使用的诊断标志物也是AC预后良好的独立生物标志物。版权所有(C) 2008大不列颠和爱尔兰病理学会。约翰·威利父子有限公司出版。
Acquired chromosomal aberrations play an important role in tumour development and progression. Such genetic alterations occur in a significant proportion of non-small cell lung carcinomas (NSCLCs) and include amplification of 14q13.3, which contains the TTF1 gene. We asked whether TTF1 amplification is associated with increased TTF1 protein expression in NSCLCs, and whether TTF1 is associated with clinicopathological features, including patient survival. We used a FISH assay and quantitative immunohistochemical staining to interrogate a population-based cohort of 538 NSCLCs from Swiss patients for TTF1 amplification and protein expression. We found TTF1 amplification in similar to 13% of adenocarcinomas (ACs) and in similar to 9% of squamous cell carcinomas (SCCs) and TTF1 amplification was associated with increased TTF1 protein expression. High-level TTF1 expression was significantly associated with smaller tumour size, female gender and longer overall survival only among ACs (median survival 82 versus 28 months; p = 0.002). On multivariate analysis, high TTF1 expression was an independent predictor of favourable prognosis in patients with AC [hazard ratio, 0.56 (95% CI 0.38-0.83); p = 0.008]. We conclude that TTF1 amplification is a mechanism of high-level TTF1 expression in a subset of NSCLCs. When expressed at high levels, this routinely used diagnostic marker is also an independent biomarker of favourable prognosis in AC. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.