Combining two biochemical techniques may help identify patients with non-small cell lung cancer (NSCLC) with rare or novel anaplastic lymphoma kinase (ALK) gene rearrangements that respond to treatment with Xalkori (crizotinib).
The two techniques are fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC).
The study, “Combinational Analysis Of FISH And Immunohistochemistry Reveals Rare Genomic Events In ALK Fusion Patterns In NSCLC And Responds To Crizotinib Treatment,” was published in the Journal of Thoracic Oncology by a group of Chinese researchers.
ALK gene rearrangements are found in 3 to 5 percent of patients with NSCLC. In these patients, cancer cells carry a fusion of the ALK gene and another gene called EML4. The resulting fusion gene codes for an abnormal protein that sends signals to the growth centers of cells telling them to divide and multiply.
The good news is that some cancers with these ALK rearrangements can be treated with drugs that block the function of the resulting abnormal protein, inhibiting the signals telling the cancer cells to divide, and thereby halting cancer growth.
Therefore, it is routine practice to screen patients with NSCLC for ALK rearrangements to assess which patients will benefit from these drugs. Traditionally, the FISH technique is used to screen patients for new ALK fusions. But there is evidence that IHC can provide sensitive and reliable identification of the fusions, including in patients that had previously been considered ALK-negative by FISH, suggesting the existence of previously unknown ALK genes.
This discrepancy led researchers to screen 3,128 patients with NSCLC for ALK rearrangements. Among them, 2,991 patients were screened using both FISH and an FDA-approved IHC assay.
The results revealed 14 patients with negative and atypical FISH but IHC positivity. These patients were then investigated using next-generation sequencing (NGS), a technique that sequences the entire DNA, to confirm the presence of ALK fusions.
This analysis revealed that eight patients had EML4-ALK fusions, and three patients had new, previously unidentified ALK rearrangements. The three other patients had no ALK fusions.
Among the 14 patients, four were treated with Xalkori (an ALK inhibitor approved for the treatment of NSCLC) and showed partial responses after the follow-up period.
“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,” Wenbin Li and colleagues wrote.
“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,” they wrote.