Epidermal growth factor receptor mutations detected by denaturing high-performance liquid chromatography in nonsmall cell lung cancer: impact on response to therapy with epidermal growth factor receptor-tyrosine kinase inhibitors.
BACKGROUND
Somatic mutations in the epidermal growth factor receptor (EGFR) kinase domain are associated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKI) in patients with nonsmall cell lung cancer (NSCLC).


METHODS
The authors tested the possibility that nucleotide sequencing may be poorly suited for detection of mutations in tumor samples and found that denaturing high-performance liquid chromatography (dHPLC) was an efficient and more sensitive method for screening.


RESULTS
These results suggested that some reports based on standard DNA sequencing techniques may have underestimated mutation rates. In the present report, the authors examined the relationship between the presence and type of EGFR mutations detected by dHPLC and various clinicopathologic features of NSCLC, including response to therapy with EGFR-TKI. Among 251 patients with advanced disease, 100 individuals received EGFR-TKI. Those whose tumors harbored a detectable EGFR kinase mutation were much more likely to have a partial response (PR) or stable disease (SD) with EGFR-TKI therapy than patients whose tumor contained no mutation (80% vs 35%; P = .001). Among the individual genotype subgroups, the frequency of a PR or SD was significantly different between patients with an exon 19 deletion compared with those with no detectable mutation (86% vs 35%; P < .001). Furthermore, patients whose tumors expressed an exon 19 mutant EGFR isoform exhibited a trend toward better EGFR-TKI response (86% vs 67%; P = .171) and improved survival compared with patients whose tumors expressed an exon 21 mutation.


CONCLUSIONS
Our findings warrant confirmation in large prospective trials and exploration of the biological mechanisms of the differences between mutation types.
Cohen
Victor
V
Segal Cancer Center, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada. vcohen@onc.jgh.mcgill.ca
Agulnik
Jason S
JS
Ang
Celina
C
Kasymjanova
Goulnar
G
Batist
Gerald
G
Small
David
D
Brandao
Guilherme
G
Chong
George
G
Miller
Wilson H
WH
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D005260:Female; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D009154:Mutation; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D066246:ErbB Receptors