Circulating Tumor Cells with ALK Rearrangement in ALK-positive NSCLC 


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The diagnostic test for ALK rearrangement in non–small cell lung cancer (NSCLC) for crizotinib (Xalkori) treatment currently uses biopsy or fine-needle aspiration. Pailler and colleagues assessed whether ALK rearrangement could be detected using circulating tumor cells. They analyzed circulating tumor cells in 18 ALK-positive and 14 ALK-negative patients using a filtration enrichment technique and filter-adapted fluorescence in situ hybridization.

All ALK-positive patients had four or more ALK-rearranged circulating tumor cells per 1 mL of blood, whereas ALK-negative patients had no or one ALK-rearranged circulating tumor cell. ALK-rearranged circulating tumor cells harbored a unique (3’5’) split pattern, whereas tumors exhibited heterogeneous split patterns (3’5’, only 3’). The ALK-rearranged circulating tumor cells also expressed a mesenchymal phenotype, in contrast with the heterogeneous epithelial and mesenchymal marker expression observed in tumors. Variations in ALK-rearranged circulating tumor cell levels were detected in the five patients being treated with crizotinib.

The investigators wrote, “ALK rearrangement can be detected in [circulating tumor cells] of patients with ALK-positive NSCLC by using a filtration technique and [filter-adapted fluorescence in situ hybridization], enabling both diagnostic testing and monitoring of crizotinib treatment. Our results suggest that [circulating tumor cells] harboring a unique ALK rearrangement and mesenchymal phenotype may arise from clonal selection of tumor cells that have acquired the potential to drive metastatic progression of ALK-positive NSCLC.” ■

Pailler E, et al: J Clin Oncol. May 13, 2013 (early release online).


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