PO-335 EGFR and ALK mutation status in advanced lung adenocarcinoma: prevalence, gender and age-related peculiarities among patients in Ukraine

Abstract

IntroductionLung adenocarcinoma is a heterogeneous group of tumours with distinct molecular characteristics. The most significant genetic alterations are EGFR mutations and ALK translocation, which prevalence, age and gender distribution are unknown in Ukrainian population of lung cancer patients. In addition, considering the appearance of new anti-ALK antibodies, the sensitivity and specificity of the IHC method for detecting ALK translocation were assessed.Material and methods267 patients with stage IV lung adenocarcinoma were included in the study. All patients underwent EGFR testing by Real-time PCR using EGFR Mutation Analysis Kit (Entrogen). 177 patients were tested for ALK translocation by FISH using ZytoLight SPEC ALK Dual Colour Break Apart Probe (Zytovision). Of these, 109 patients were co-tested for ALK by IHC using anti-ALK antibody clone 5A4 (Novocastra, Leica).Results and discussionsEGFR mutations and ALK translocation were mutually exclusive among observed patients. EGFR mutations were detected in 52 patients (19.5%). The most of cases demonstrated exon 19 deletion (61%); in 27% patients L858R mutation was detected: 4% showed exon 20 insertion; 4% - G719X mutation; 2% - G719X+exon 20 insertion; 2% L858R+T790M (during anti-EGFR TKI treatment). EGFR mutations were more often found in women rather than men (68.25% vs 7.3%; p<0,0001), with no relation to age. ALK translocation was found by FISH in 17 patients (9.6%). There was no relation to sex, however, the strong association with age was found (p=0.0018): ALK-translocation were more often among patients under 50 y.o. Moreover, this relationship was significant among females only (p=0.0175). Assessment of ALK testing by IHC and FISH revealed high concordance between these methods. The accuracy of IHC method was 92.66% (95% CI 86.05% to 96.78%). The negative predictive value was high (98.85%), however the positive predictive value (PPV) was only 68.18% due to false positive results, that requires an additional assessment of IHC-positive samples by FISH.ConclusionThe prevalence of EGFR mutations and ALK translocation among observed patients with advanced lung adenocarcinoma was quite high (19.5% and 9.6%, respectively). EGFR mutations were more common in women comparing with men, whereas ALK translocation was associated with younger age. High accuracy of ALK-detection by IHC allows using it for screening, however due to low PPV, ALK-positive IHC results should be verified by FISH.