Combining fluorescence in situ hybridization (FISH) analysis and immunohistochemistry (IHC) assays may help to identify rare anaplastic lymphoma kinase (ALK) mutations in patients with non-small cell lung cancer (NSCLC), according to a study published in the Journal of Thoracic Oncology.
The identification of ALK mutations in patients has become a critical part of NSCLC care as the development of ALK inhibitors have emerged as a therapeutic regimen capable of providing remarkable benefit to patients. As of now, there are three conventional diagnostics for ALK fusions: fluorescence in situ hybridization (FISH), real-time reverse transcription-PCR (RT-PCR), and immunohistochemistry (IHC).
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In a study led by Wenbin Li, Peking Union Medical College (Beijing, China), researchers screened 3128 patients with NSCLC for ALK fusion using both FISH analysis and IHC assays to demonstrate the importance of combining the two methods during pathological diagnosis.
The overall positivity for ALK IHC and FISH were 7.3% (228 patients) and 6.8% (214 patients), respectively. Additionally, 14 cases demonstrated positive IHC with negative or atypical FISH results. These patients were then investigated using next-generation sequencing—a technique that sequences the entire DNA—to confirm the presence of ALK fusions.
This analysis revealed that 8 patients had cancer cells carrying a fusion of the ALK gene and another gene called EML4, which has been known to be a source of cancer growth and progression. Of the 6 other patients, 3 had unidentified ALK rearrangements and 3 had no ALK fusions at all. All 14 patients were treated with crizotinib at a dose of 250mg twice per day and achieved partial response.
“The most valuable finding of our study was that patients with EML4-ALK fusion or other novel complicated rearrangements could test negative via FISH and positive via IHC and these patients could possibly benefit from ALK-targeted therapy,” Dr Li Li and colleagues concluded. “Based on these findings, combinational assay of FISH and IHC methods are highly recommended in routine pathological diagnosis and when negative and atypical FISH patterns are accompanied by positivity in IHC.”
