Identification of EGFRMutations by Immunohistochemistry with EGFRMutation–Specific Antibodies in Biopsy and Resection Specimens from Pulmonary Adenocarcinoma
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Purpose Mutation-specific antibodies have recently been developed for identification of epidermalgrowth factor receptor (EGFR) mutations by immunohistochemistry (IHC). This study wasdesigned to investigate whether the type of specimen (biopsy vs. resection) would make adifference in determining mutation status by IHC, and to evaluate whether biopsies are suitablefor detection of mutant EGFR protein. Materials and MethodsIHC was performed using mutation-specific antibodies for E746-A750 deletion (DEL) andL858R point mutation (L858R) in biopsies and tissue microarrays of resected tumors from154 patients with pulmonary adenocarcinoma. Results were then compared with DNAsequencing data. ResultsMolecular-based assays detected EGFR mutations in 62 patients (40.3%), including 14(9.1%) with DEL, and 31 (20.1%) with L858R. IHC with two mutation-specific antibodiesshowed a homogeneous staining pattern, and correctly identified EGFRmutation status in89% (137/154). Overall (biopsy/resection) sensitivity, specificity, positive predictive value,and negative predictive value were 75.6% (78.3%/72.7%), 94.5% (90.9%/96.3%), 85%(78.3%/88.9%), and 90.4% (90.9%/89.7%), respectively. ConclusionOur data showed that IHC using EGFR mutation–specific antibodies is useful for detectionof EGFRmutations with high specificity and good sensitivity not only for resection specimensbut also for biopsy materials. Therefore, IHC using EGFRmutation–specific antibodies maypreclude a second biopsy procedure to obtain additional tissues for identification of EGFRmutations by molecular assays in biopsies from advanced cancer, particularly when tumorcells in the samples are limited.
Abstract
Purpose Mutation-specific antibodies have recently been developed for identification of epidermalgrowth factor receptor (EGFR) mutations by immunohistochemistry (IHC). This study wasdesigned to investigate whether the type of specimen (biopsy vs. resection) would make adifference in determining mutation status by IHC, and to evaluate whether biopsies are suitablefor detection of mutant EGFR protein. Materials and MethodsIHC was performed using mutation-specific antibodies for E746-A750 deletion (DEL) andL858R point mutation (L858R) in biopsies and tissue microarrays of resected tumors from154 patients with pulmonary adenocarcinoma. Results were then compared with DNAsequencing data. ResultsMolecular-based assays detected EGFR mutations in 62 patients (40.3%), including 14(9.1%) with DEL, and 31 (20.1%) with L858R. IHC with two mutation-specific antibodiesshowed a homogeneous staining pattern, and correctly identified EGFRmutation status in89% (137/154). Overall (biopsy/resection) sensitivity, specificity, positive predictive value,and negative predictive value were 75.6% (78.3%/72.7%), 94.5% (90.9%/96.3%), 85%(78.3%/88.9%), and 90.4% (90.9%/89.7%), respectively. ConclusionOur data showed that IHC using EGFR mutation–specific antibodies is useful for detectionof EGFRmutations with high specificity and good sensitivity not only for resection specimensbut also for biopsy materials. Therefore, IHC using EGFRmutation–specific antibodies maypreclude a second biopsy procedure to obtain additional tissues for identification of EGFRmutations by molecular assays in biopsies from advanced cancer, particularly when tumorcells in the samples are limited.
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