Club – AC Roden

Results:  52.9% men, 57.5% smokers, acinar predominant most prevalent  EGFR mutation in 46.3% (55.9% 19del including 30.6% E746_A750 del; 41.4% L858R)  Interobserver variability for E746_A750del-specific ab: =0.86 (if score ≥2 considered +), =0.95 (score 3+), =0.43 (all scores)  Interobserver variability for L858R-specific protein ab: =0.73 (if score ≥2 considered +), =0.97 (score 3+), =0.48 (all scores)  E746_A750 del-specific protein – cytoplasmic and/or membranous, + in 34 cases (16.7%); score 1 (14), 2 (16), 3 (10)  L858R-specific protein – cytoplasmic and/or membranous, 2 cases nuclear staining, + in 58.3% (score 1 (83), 2 (38), 3 (19)  Intratumoral heterogeneity in 3% (E746_A750 del) and 4.7% (L858R)  Correlation protein expression mutation: E746_A750-mutated cases (n=34): IHC 3+ (29.4%), 2+ (41.2%), 1+ (23.5%), 0 (5.9%). E746_A750-wt cases (n=28): IHC score 0 (93%), 1+ (4%), 2+ (4%); the cases with score 1+ & 2+ (n=2) had L747 T751 deletion in exon 19 L858R-mutated cases (n=46): IHC 3+ (41.3%), 2+ (39.1%), 1+ (13.0%), 0 (6.5%). Sensitivity, specificity, PPV, and NPV for IHC (cutoff score 2): E746 A750 del: 70.6%, 99.0%, 92.3%, 95.3%. 19 del in total: 40.3%, 99.4%, 96.2%, 82.7%. L858R: 80.4%, 89.7%, 64.9%, 95.1%. If score 3 is cutoff – specificity and PPV for both ab is 100%  If IHC scores of 2 & 3 considered positive: No difference in outcome between IHC-EGFR+ and – groups and between EGFR mutant and wt groups. For EGFR wt group: patients with EGFR-IHC + had longer PFS (p=0.033); no statistical difference in multivariate analysis