Concordance of IHC, FISH and RT-PCR for EML4-ALK rearrangements
Cristina Teixidó1, Niki Karachaliou1, Vicente Peg1
11 Pangaea Biotech, Quirón Dexeus University Institute, 08028 Barcelona, Spain, 2 Dr Rosell Oncology Institute, Quirón Dexeus University Institute, 08028 Barcelona, Spain ; 3 Catalan Institute of Oncology, Hospital Germans Trias i Pujol, 08916 Badalona, Spain.
Abstract:
The echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) has emerged as the second most important driver oncogene in lung cancer and the first targetable fusion oncokinase to be identified in 4-6% of lung adenocarcinomas. Crizotinib, along with a diagnostic test-the Vysis ALK Break Apart fluorescence in situ hybridization (FISH) Probe Kit-is approved for the treatment of ALK positive advanced non-small cell lung cancer (NSCLC). However, the success of a targeted drug is critically dependent on a sensitive and specific screening assay to detect the molecular drug target. In our experience, reverse transcription polymerase chain reaction (RT-PCR)-based detection of EML4-ALK is a more sensitive and reliable approach compared to FISH and immunohistochemistry (IHC). Although ALK FISH is clinically validated, the assay can be technically challenging and other diagnostic modalities, including IHC and RT-PCR should be further explored.
Insights
Reverse transcription polymerase chain reaction (RT-PCR) offers a more sensitive and reliable method for detecting the EML4-ALK fusion oncokinase in lung cancer compared to FISH and IHC. Further exploration of RT-PCR and IHC as diagnostic tools is recommended.
Area of Science:
- Oncology
- Molecular Biology
- Diagnostics
Background:
- The echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) fusion oncokinase is a key driver in lung adenocarcinoma.
- ALK-positive non-small cell lung cancer (NSCLC) is targetable with drugs like Crizotinib.
- Accurate detection of the EML4-ALK fusion is crucial for effective targeted therapy.
Purpose of the Study:
- To compare the sensitivity and reliability of different diagnostic methods for detecting the EML4-ALK fusion.
- To evaluate reverse transcription polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC) for EML4-ALK detection.
Main Methods:
- Comparative analysis of diagnostic techniques including RT-PCR, FISH, and IHC.
- Assessment of assay sensitivity and reliability in detecting EML4-ALK.
Main Results:
- RT-PCR demonstrated higher sensitivity and reliability for EML4-ALK detection compared to FISH and IHC.
- FISH, while clinically validated, presents technical challenges.
Conclusions:
- RT-PCR is a more sensitive and reliable method for diagnosing EML4-ALK positive NSCLC.
- Further investigation into IHC and RT-PCR as complementary or alternative diagnostic modalities is warranted.
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