Epidermal growth factor receptor mutations detected by denaturing high‐performance liquid chromatography in nonsmall cell lung cancer

Abstract

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. Cancer 2010. © 2010 American Cancer Society.

Distribution of EGFR Mutations Commonly Observed in Primary Lung Adenocarcinomas in Pakistan as Predictors for Targeted Therapy

“…As compared to other studies which showed that adenocarcinoma is more common in female (Wang et al, 2011), our study could not comment yet because of small size of the cases tested. Overall prevalence of EGFR mutation slightly matched with reported Asian data which ranges between 27-60% in various studies (Cohen et al, 2010).Another similarity in our data with Western and Asian data is the highest mutation rate of 48% noted for L858R (exon 21) followed by deletions of exon 19 (44%) of EGFR mutant isoform.…”

Screening for EGFR mutations in lung cancer, a report from India

“…Our overall prevalence of mutation being 51% matches with other reporting of East Asian data of 27-60% [15]. Recent studies suggests patients whose tumors expressed an exon 19 mutant EGFR isoform exhibited a trend towards better EGFR-TKI response (86% vs 67%; p = .171) and improved survival compared with patients whose tumors expressed an exon 21 mutation [24]. This suggests that major subset of Indian population affected with lung cancer would be benefited by TKI therapy due to the increased prevalence of these mutations.…”

Standardization of Epidermal Growth Factor Receptor (EGFR) Measurement by Quantitative Immunofluorescence and Impact on Antibody-Based Mutation Detection in Non–Small Cell Lung Cancer

“…24,41,42 Use of antibodies that are specific to mutated protein present a potentially less expensive and more routine method for mutation detection. However, new technologies and methods may soon neutralize any cost difference between DNA and protein analyses.…”