组织和血清 EGFR 作为恶性胸膜间皮瘤的预后因素。
Tissue and serum EGFR as prognostic factors in malignant pleural mesothelioma.
机构信息
Medical Oncology Department, National Cancer Institute, Cairo University, Egypt.
出版信息
Lung Cancer. 2010 Oct;70(1):43-50. doi: 10.1016/j.lungcan.2010.01.002. Epub 2010 Mar 27.
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 EGFR 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 (++, +++) EGFR 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 EGFR 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.
背景
恶性胸膜间皮瘤（MPM）是一种与石棉有关的侵袭性肿瘤。石棉会导致基因改变和细胞信号事件，从而有利于对化疗的耐药性。已经确定了多种受体酪氨酸激酶在肿瘤发生的各个方面发挥核心作用。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度表达，其中 EGFR 异常不仅预测对 EGFR 酪氨酸激酶抑制剂的反应，而且还指示肿瘤进展。然而，在 MPM 中，EGFR 的作用尚不明确。本研究旨在鉴定 MPM 患者的血清和组织 EGFR 水平，并评估血清和组织 EGFR 水平与临床病理预后因素和生存之间的关系。
方法
我们调查了 71 例 MPM 患者的组织中 EGFR 的表达。在其中的 40 例中评估了血清 EGFR，另外 20 例健康受试者作为对照。使用定量酶联免疫吸附试验（ELISA）检测治疗前血清 EGFR 水平。通过免疫组化评估组织 EGFR 蛋白过表达，通过原位杂交（CISH）技术评估基因扩增。结果与患者的临床病理因素和总生存期（OS）相关。
结果
在纳入研究的 71 例患者中，有 19 例接受了胸膜外全肺切除术。其余 46 例患者接受了化疗，6 例患者仅接受了最佳支持治疗。在 74.6%的病例中检测到 EGFR 免疫反应，37 例（52.1%）病例通过 CISH 检测到 EGFR 基因扩增，其中 31 例显示中到高强度（+++，++++）EGFR 免疫反应。45%的病例报告了血清 EGFR 升高>2.5ng/ml（MPM 中 EGFR 的中位数浓度）。46 例接受化疗的治疗患者的总体缓解率（RR）为 24.1%。中位随访 29 个月后，中位总生存期（OS）为 10 个月。血清和组织中 EGFR 的升高与疾病晚期显著相关。然而，组织中 EGFR 过表达或高血清水平与生存率均无关。
结论
EGFR 表达是 MPM 患者的常见特征。治疗前高血清 EGFR 水平与晚期疾病相关，但与降低的 OS 无关。仍需要对大量患者进行详细的 EGFR 突变分析，以明确 EGFR 在 MPM 患者中的确切作用。
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