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Epidermal growth factor receptor (EGFR) gene mutations are usually detected by direct sequencing to identify patients with advanced pulmonary adenocarcinomas as candidates for tyrosine kinase inhibitor therapy. The aim of the study was to evaluate the efficacy of EGFR mutation-specific antibodies in identifying EGFR-mutated adenocarcinomas.Thirty-three consecutive cases of pulmonary adenocarcinomas sequenced for EGFR mutations were retrieved from our files. Immunohistochemistry was performed with the rabbit monoclonal antibodies E746-A750del (6B6) and L858R (43B2). The results obtained using the 2 procedures were statistically compared by Coehn κ and by calculation of sensitivity and specificity.There were 21 women and 12 men, ranging in age from 48 to 78 years. All cases were lung adenocarcinomas, 23 primaries and 10 metastatic. The mutational spectrum was as follows: 12 cases mutated in exon 19 (9 with E746-A750del, 1 with homozygote L747-T751del, 1 with L747-P753del, 1 with E747-S752del), 6 in exon 21 (5 with L858R, 1 with L861Q+L862L), and 15 EGFR wild type. Immunohistochemistry detected 6/9 cases with an E746-A750del mutation (κ=0.744, sensitivity: 66.7%, specificity: 100%) and 5/5 cases with an L858R mutation (κ=1, sensitivity: 100%, specificity: 100%). Four cases showed faint and focal immunostaining and were interpreted as negative. All other cases were negative. Overall, the 2 antibodies had 61.1% sensitivity and 100% specificity for EGFR mutations.EGFR mutation-specific antibodies may represent a first-line screening tool to identify patients as candidates for tyrosine kinase inhibitor therapy.