Tissue and serum EGFR as prognostic factors in malignant pleural mesothelioma
Tissue and serum EGFR as prognostic factors in malignant pleural mesothelioma
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DOI：
10.1016/j.lungcan.2010.01.002
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发表时间：
2010-10-01
期刊：
影响因子：
5.3
通讯作者：
Mokhtar, Nadia
中科院分区：
文献类型：
--
作者：
Gaafar, Rabab;Bahnassy, Abeer;Mokhtar, Nadia
背景：恶性胸膜间皮瘤（MPM）是一种石棉相关的侵袭性肿瘤。天冬氨酸导致基因修饰和细胞信号事件，有利于对化疗的抵抗。已经鉴定出多种受体酪氨酸激酶在肿瘤发生的各个方面发挥中心作用。表皮生长因子受体（EGFR）在包括肺癌在内的多种上皮恶性肿瘤中过表达，其中EGFR畸变不仅预测对EGFR酪氨酸激酶抑制剂的反应，而且指示肿瘤进展。然而，在MPM中，EGFR的作用不太清楚。本研究旨在确定MPM患者血清和组织中EGFR水平，并评估血清和组织中EGFR水平与临床病理预后因素和生存率之间的关系。对其中40例进行EGFR检测，并与20例健康体检者进行对照。采用定量酶联免疫吸附试验测定治疗前血清EGFR水平。组织埃格蛋白的过度表达通过免疫组织化学和基因扩增进行了评估，通过色原原位杂交（CISH）技术。结果：71例患者中，19例行胸膜外全肺切除术，11例未行胸膜外全肺切除术，1例未行胸膜外全肺切除术，1例未行胸膜外全肺切除术，1例未行胸膜外全肺切除术。其余46例接受化疗，6例仅接受最佳支持治疗。74.6%的病例EGFR免疫反应阳性，CISH扩增阳性37例（52.1%），其中31例为中~高（++，+）埃格免疫反应。45%的病例报告血清EGFR升高>2.5 ng/ml（MPM中EGFR的中位浓度）。46例接受化疗的患者的总有效率（RR）为24.1%。中位随访29个月后，中位总生存期（OS）为10个月。血清和组织EGFR升高与晚期疾病阶段显著相关。然而，无论是组织中的埃格过表达，也没有高水平的血清EGER与生存率。结论：EGFR表达是一个共同的特点，在MPM患者。高治疗前血清EGFR水平与晚期相关，但与OS降低无关。仍需要对大量患者进行EGFR突变的详细分析，以阐明EGFR在MPM患者中的确切作用。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Background: Malignant pleural mesothelioma (MPM) is an asbestos related aggressive tumor. Asbestos causes genetic modifications and cell signaling events that favor resistance to chemotherapy. A variety of receptor tyrosine kinases have been identified to play a central role in various aspects of tumorigenesis. Epidermal growth factor receptor (EGFR) is overexpressed in a variety of epithelial malignancies including lung cancer in which EGFR aberrations not only predict response to EGFR tyrosine kinase inhibitors but also indicate tumor progression. However in MPM, the role of EGFR is less clear. This study was designed to identify serum and tissue EGFR levels in patients with MPM and to evaluate the relationship between serum and tissue EGFR levels and clinicao-pathological prognostic factors and survival.Methods: We investigated 71 cases of MPM for EGFR expression in tissue. Serum EGFR was assessed in 40 out of those 71 cases and 20 healthy subjects as a control. Pre-treatment serum EGFR levels were measured using quantitative enzyme-linked immunosorbent assay. Tissue EGER protein overexpression was assessed by immunohistochemistry and gene amplification was assessed by the chromogen in situ hybridization (CISH) technique. Results were correlated with the clinical-pathological factors of the patients and overall survival (OS).Results: Out of the 71 patients included in the study, 19 had undergone extrapleural pneumonectomy. As for the rest of the patients, 46 received chemotherapy while 6 had only best supportive care. EGFR immuno-reactivity was detected in 74.6% of the cases, 37 (52.1%) cases were positive for EGFR gene amplification by CISH, 31 of them revealed moderate to high (++, +++) EGER immuno-reactivity. Elevated serum EGFR >2.5 ng/ml (the median concentration of EGFR in MPM) was reported in 45% of the cases. The overall response rate (RR) for the 46 treated patients who received chemotherapy was 24.1%. After a median follow up of 29 months, the median overall survival (OS) was 10 months. Elevated serum and tissue EGFR is significantly associated with advanced disease stage. However neither EGER overexpression in tissues nor high serum levels were associated with survival rates.Conclusions: EGFR expression is a common feature in MPM patients. High pre-treatment levels of serum EGFR are associated with advanced stage but not with reduced OS. Detailed mutational analysis of EGFR on a larger number of patients is still needed to clarify the exact role of EGFR in MPM patients. (C) 2010 Elsevier Ireland Ltd. All rights reserved.