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Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
[Value of Immunohistochemical Methods in Detecting EML4-ALK Fusion Mutations: A Meta-analysis]
Chang Liu1, Lu Cai1, Diansheng Zhong1
1Department of Medical Oncology, Tianjin Medical University General Hospital, Tianjin 300052, China.
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.
Insights
Immunohistochemistry (IHC) is a sensitive and specific method for detecting echinoderm microtubule-associated protein 4 (EML4)-anaplastic lymphatic tumor kinase (ALK) fusion mutations. This technique offers a rapid and valuable approach for screening non-small cell lung cancer patients for targeted therapy.
Area of Science:
- Oncology
- Molecular Diagnostics
- Biomarker Detection
Background:
- The echinoderm microtubule-associated protein 4 (EML4)-anaplastic lymphatic tumor kinase (ALK) fusion gene occurs in approximately 5% of non-small cell lung cancer (NSCLC) cases.
- ALK rearrangements are crucial targets for NSCLC therapy, with ALK inhibitors achieving up to 80% disease control rates.
- Accurate and rapid detection of EML4-ALK fusion is essential for patient selection in personalized molecular therapy.
Purpose of the Study:
- To evaluate the sensitivity and specificity of immunohistochemistry (IHC) for detecting EML4-ALK fusion mutations.
- To assess the accuracy and clinical utility of IHC compared to fluorescence in situ hybridization (FISH).
- To provide a basis for the clinical application of IHC in NSCLC molecular therapy.
Main Methods:
- A systematic literature search was conducted on the PubMed database up to February 25, 2015.
- Meta-analysis of diagnostic tests was employed to compare the performance of IHC against FISH.
- Inclusion and exclusion criteria were applied to screen relevant studies for the meta-analysis.
Main Results:
- The meta-analysis included 11 studies with a total of 3,234 cases.
- The diagnostic odds ratio (DOR) for IHC was 1,135.00 (95% CI: 337.10–3,821.46).
- The summary receiver operating characteristic (SROC) curve showed a high area under the curve (AUC) of 0.992 and a Q* value of 0.964.
Conclusions:
- Immunohistochemistry (IHC) is a feasible method for detecting EML4-ALK fusion gene mutations using specific antibodies.
- IHC demonstrates high sensitivity and specificity for identifying EML4-ALK fusion.
- IHC serves as a simple, rapid, and clinically valuable tool for screening EML4-ALK fusion gene mutations in NSCLC patients.
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