Identification of EGFR Mutations by Immunohistochemistry with EGFR Mutation–Specific Antibodies in Biopsy and Resection Specimens from Pulmonary Adenocarcinoma

PURPOSE: Mutation-specific antibodies have recently been developed for identification of epidermal growth factor receptor (EGFR) mutations by immunohistochemistry (IHC). This study was designed to investigate whether the type of specimen (biopsy vs. resection) would make a difference in determining mutation status by IHC, and to evaluate whether biopsies are suitable for detection of mutant EGFR protein. MATERIALS AND METHODS: IHC was performed using mutation-specific antibodies for E746-A750 deletion (DEL) and L858R point mutation (L858R) in biopsies and tissue microarrays of resected tumors from 154 patients with pulmonary adenocarcinoma. Results were then compared with DNA sequencing data. RESULTS: Molecular-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 antibodies showed a homogeneous staining pattern, and correctly identified EGFR mutation status in 89% (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. CONCLUSION: Our data showed that IHC using EGFR mutation–specific antibodies is useful for detection of EGFR mutations with high specificity and good sensitivity not only for resection specimens but also for biopsy materials. Therefore, IHC using EGFR mutation–specific antibodies may preclude a second biopsy procedure to obtain additional tissues for identification of EGFR mutations by molecular assays in biopsies from advanced cancer, particularly when tumor cells in the samples are limited.