Abstract: Background and purpose: Epidermal growth factor receptor (EGFR) gene mutation is the most important predictive factor for determining the effectiveness of EGFR tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC). This study aimed to determine the clinical application value of mutation-specific immunohistochemistry for EGFR mutation detection in NSCLC. Methods: Mutation-specific immunohistochemistry and amplification refractory mutation system (ARMS) were used simultaneously to detect EGFR gene mutation status in 290 lung cancer specimens. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of mutation-specific immunohistochemistry for detecting EGFR gene mutations were evaluated. The consistency was analyzed between mutation-specific immunohistochemistry results and ARMS results. Results: With ARMS testing as the gold standard, when a cutoff value of score 1+ was used as positive by immunohistochemistry, the sensitivity of mutation-specific immunohistochemistry for EGFR gene mutation was 72.92%, specificity 95.20%, positive predictive value 93.75% and negative predictive value 78.08%. The accuracy of immunohistochemistry was obviously different  when various EGFR gene mutations were detected. The sensitivity of immunohistochemistry for exon 19 deletion was only 55.55%, but specificity was above 99%. When immunohistochemistry score was 1+, the sensitivity for L858R mutation was 90.27%, whereas specificity was 95.86%. When immunohistochemistry score was 2+ or 3+, the specificity for L858R mutation was 98.63%-100%. The results of mutation-specific immunohistochemistry were finely correlated with mutation status determined by ARMS assay (P<0.001, Kappa value: 0.612-0.864). Mutation-specific immunohistochemistry can directly determine EGFR gene mutation abundance at the cellular level. Conclusion: Mutation-specific immunohistochemistry could be an effective supplemental method to EGFR molecular tests.

Key words: Non-small cell lung cancer, Epidermal growth factor receptor, Mutations, Immunohistochemistry