Maheswaran S et al. (2008) Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 359: 366–377

Despite the dramatic responses to EGFR therapy observed in patients with non-small-cell lung cancers (NSCLC) that harbor activating mutations in EGFR, the majority of patients relapse—often because their tumors acquire secondary EGFR mutations. Maheswaran and colleagues evaluated the ability of a microfluid cell-capture chip, which contains microposts coated with antibodies against epithelial-cell adhesion molecules, to isolate circulating tumor cells (CTCs) from patients with NSCLC.

The device successfully isolated CTCs (median 74 cells/ml) from each of 27 patients with advanced NSCLC. These isolated CTCs were then used in mutational analysis of EGFR. The presence of the EGFR T790M mutation, which confers drug resistance, in pretreatment tumor specimens was associated with greatly reduced progression-free survival compared with tumor specimens that lacked this mutation (7.7 months and 16.5 months, respectively; P <0.001). The EGFR activating mutation was identified in 11 of 12 patients for whom CTCs, plasma samples and primary tumor specimens were available. CTC genotyping, therefore, had 92% sensitivity to detect such mutations, whereas plasma genotyping (which identified mutations in 4 of 12 patients) had 33% sensitivity (P = 0.009). Moreover, increased CTC numbers were associated with clinical progression and the emergence of additional EGFR mutations after therapy. Conversely, a decline in CTC numbers was associated with a radiographically evident response to therapy.

The authors suggest that the cell-capture chip can reliably isolate CTCs in an acceptable quantity and with satisfactory purity for use in molecular studies.