Detection of EGFR gene mutations with mutation-speciifc immunohistochemistry in non-small cell lung cancer / 中国癌症杂志

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-speciifc immu-nohistochemistry forEGFR mutation detection in NSCLC.Methods:Mutation-specific immunohistochemistry and ampliifcation refractory mutation system (ARMS) were used simultaneously to detectEGFR gene mutation status in 290 lung cancer specimens. The sensitivity, speciifcity, positive predictive value (PPV) and negative predictive value (NPV) of mutation-speciifc immunohistochemistry for detectingEGFR gene mutations were evaluated. The consistency was analyzed between mutation-speciifc 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-speciifc immunohistochemistry forEGFR gene mutation was 72.92%, speciifcity 95.20%, positive predictive value 93.75% and negative predictive value 78.08%. The accuracy of immunohistochemistry was obviously different when variousEGFR gene mutations were detected. The sensitivity of immunohistochemistry for exon 19 deletion was only 55.55%, but speciifcity was above 99%. When immunohistochemistry score was 1+, the sensitivity for L858R mu-tation was 90.27%, whereas speciifcity was 95.86%. When immunohistochemistry score was 2+ or 3+, the speciifcity for L858R mutation was 98.63%-100%. The results of mutation-speciifc immunohistochemistry were ifnely correlated with mutation status determined by ARMS assay (P<0.001, Kappa value 0.612-0.864). Mutation-speciifc immunohis-tochemistry can directly determineEGFR gene mutation abundance at the cellular level.Conclusion:Mutation-speciifc immunohistochemistry could be an effective supplemental method toEGFR molecular tests.