Background and objective: The fusion between echinoderm microtubule-associated protein 4 (EML4) and anaplastic lymphatic tumor kinase (ALK) rearrangement is present in approximately 5% of non-small cell lung cancer (NSCLC) patients. It has been regarded as another new target gene after epidermal growth factor receptor (EGFR) and K-ras. Figures showed that the disease control rate could reach up to 80% in NSCLC patients with EML4-ALK fusion gene after treated with ALK inhibitors. Thus, exploring an accurate and rapid detecting method is the key in screening NSCLC patients with EML4-ALK expressions. The aim of this study is to analyze the specificity and sensitivity of IHC in detecting EML4-ALK fusion mutations. To evaluate the accuracy and clinical value of this method, and then provide basis for individual molecular therapy of NSCLC patients.
Methods: Using Pubmed database to search all documents required. The deadline of retrieval was February 25, 2015. Then further screening the articles according to the inclusion and exclusion criteria. Using diagnostic test meta-analysis methods to analyze the sensitivity and specificity of the immunohistochemistry (IHC) method compared with fluorescence in situ hybridization (FISH) method.
Results: Eleven literatures were added into the meta analysis, there were 3,234 of total cases. The diagnostic odds ratio (DOR) was 1,135.00 (95%CI: 337.10-3,821.46); the area under curve (AUC) of summary receiver operating characteristic curve (SROC) curve was 0.992,3 (SEAUC=0.003,2), the Q* was 0.964,4 (SEQ*=0.008,7).
Conclusions: Immunohistochemical detection of EML4-ALK fusion gene mutation with specific antibody is feasible. It has high sensitivity and specificity. IHC can be a simple and rapid way in screening EML4-ALK fusion gene mutation and exhibits important clinical values.
背景与目的 棘皮动物微管相关蛋白4（echinoderm microtubule-associated protein 4, EML4）与间变性淋巴瘤激酶（anaplastic lymphatic tumor kinase, ALK）重排形成的融合基因存在于大约5%的非小细胞肺癌（non-small cell lung cancer, NSCLC）患者中，是继表皮生长因子受体（epidermal growth factor receptor, EGFR）、K-ras之后又一新型靶点基因。有数据显示携带EML4-ALK融合基因的NSCLC患者接受ALK抑制剂治疗后，其疾病控制的有效率可达80%，探索和建立能够准确快速检测出NSCLC患者EML4-ALK融合突变的方法，是筛选出适合治疗的优势人群的关键。本研究分析免疫组化法（immunohistochemistry, IHC）检测EML4-ALK融合基因突变的敏感度与特异度，评价该方法准确性及临床应用价值，从而为肺癌患者“个体化分子治疗”提供依据。方法 通过Pubmed数据库检索所有符合检索条件的文献，末次检索日期为2015年2月25日，根据纳入和排除标准进行进一步筛选，采用诊断试验meta分析方法，比较特异性抗体免疫组化法与“金标准”荧光原位杂交（fluorescence in situ hybridization, FISH）法的敏感度、特异度，以明确特异性抗体IHC作为筛查方法的可行性。结果 本文11篇文献纳入meta分析，EML4-ALK融合基因免疫组化累计病例3,234例，诊断比值比（diagnositic odds ratio, DOR）为1,135.00（95%CI: 337.10-3,821.46）；综合受试者工作特征曲线 （summary receiver operating characteristic curve, SROC）下面积为0.992,3（SEAUC=0.003,2），Q*统计量为0.964,4（SEQ*=0.008,7）。结论 特异性抗体IHC法检测EML4-ALK融合基因的方法可行，具有高特异度和敏感度，可作为一种简单快速的筛查方法，具有临床应用价值。.