PTEN expression is a strong predictor of survival in mesothelioma patients
PTEN expression is a strong predictor of survival in mesothelioma patients
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DOI：
10.1016/j.ejcts.2007.09.045
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发表时间：
2008-03-01
影响因子：
3.4
通讯作者：
Weder, Walter
中科院分区：
文献类型：
--
作者：
Opitz, Isabelle;Soltermann, Alex;Weder, Walter
背景：恶性胸膜间皮瘤（MPM）是一种高度侵袭性的肿瘤，预后差，对治疗反应有限。MPM的特征是复杂的染色体畸变，包括10号染色体丢失。位于染色体10 q23上的肿瘤抑制基因磷酸酶和张力蛋白同源物10号染色体缺失（PTEN）在不同的癌症中起着重要作用，但其与MPM的相关性尚不清楚。患者及方法：在本组织芯片为基础的研究中，341 MPM的PTEN表达进行了研究，通过免疫组化使用单克隆小鼠PTEN抗体。对表达水平进行半定量评分（阴性、弱、中度、强）。PTEN的表达与总生存期相关。结果：206例患者的临床数据可用。105例患者为T4期，92例患者出现区域和纵隔淋巴结转移。在62%的病例中观察到PTEN表达缺失。在126例随访资料完整的病例中，生存时间与PTEN表达相关。比较任何PTEN表达与无表达，具有PTEN表达的患者的中位生存时间显著更长（对数秩检验p = 0.0001）（15.5个月; 95%Cl：3.8; 27.2 vs 9.7个月; 95%Cl：7.9; 11.7）。考克斯回归分析显示，PTEN表达与存活率之间的相关性（p = 0.003）独立于组织学亚型（p = 0.7）。结论：PTEN是间皮瘤患者独立的预后标志物。肿瘤抑制基因PTEN表达的频繁波动表明PI 3 K-AKT/蛋白激酶B（PKB）通路参与MPM，这可能与未来间皮瘤治疗相关。(c)2008年欧洲胸外科协会。Elsevier B. V.出版，保留所有权利。
Background: Malignant pleural mesothelioma (MPM) is a highly aggressive tumour with poor prognosis and Limited response to therapy. MPM is characterised by complex chromosomal aberrations, including chromosome 10 losses. The tumour suppressor gene phosphatase and tensin homologue deleted from chromosome 10 (PTEN) located on chromosome 10q23 plays an important role in different cancer, but its relevance for MPM is unclear. Patients and methods: In the present tissue microarray-based study, 341 MPM were studied for PTEN expression by immunohistochemistry using a monoclonal mouse PTEN antibody. Expression levels were semiquantitatively scored (negative, weak, moderate, strong). Expression of PTEN was correlated to overall survival. Results: Clinical data from 206 patients were available. One hundred and five patients were stage T4 and 92 patients presented with regional and mediastinal lymph node metastasis. Loss of PTEN expression was observed in 62% of the cases. The survival time was correlated to PTEN expression in 126 cases with complete follow-up data. Comparing any PTEN expression versus no expression, median survival time was significantly Longer (log rank test p = 0.0001) in patients with PTEN expression (15.5 months; 95% Cl: 3.8; 27.2 vs 9.7 months; 95% Cl: 7.9; 11.7). Cox regression analysis revealed an association between PTEN expression and survival to = 0.003) independently from the histological subtype (p = 0.7). Conclusion: PTEN is an independent prognostic biomarker in mesothelioma patients. The frequent toss of expression of the tumour suppressor gene PTEN suggests involvement of the PI3K-AKT/protein kinase B (PKB) pathway in MPMs, which may be relevant for future mesothelioma treatment. (c) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.