In the early phase trial of crizotinib, approximately 1500 patients were screened by FISH to identify 82 ALK-positive patients. The large number of patients qualifying for screening underscores the need for a high throughput and cost- effective screening modality. "An optimal assay should therefore not only be sensitive and specific, but also be economical, easy to perform, preferably automated, and readily adaptable to workflows of clinical service laboratories," continue the investigators.
To explore alternative screening modalities for detecting ALK fusions, they designed a novel method for detecting ALK fusions by direct, multiplexed transcript profiling using the gene expression platform from NanoString. They tested their assay in 66 archival NSCLC samples which had been independently tested by both FISH and IHC methods in terms of sensitivity, specificity, reproducibility, and concordance to prior FISH and IHC.
The results were highly concordant to previous results obtained by FISH and IHC and the investigators were able to successfully detect low-level ALK fusion transcripts in samples with low tumor cell content. All samples predicted to be positive in the assay responded favorably to crizotinib.
"While further testing on a larger sample size is needed for this assay to be considered in clinical practice, we have demonstrated that it offers a cost-effective, easy to perform, high-throughput, and FFPE-compatible screening alternative for detecting ALK fusions," conclude the investigators.
|Contact: David Sampson|
Elsevier Health Sciences