ABSTRACT Treatment of non-small cell carcinoma (NSCC) has transformed with the identification of molecular alterations with differing responses to targeted therapies. In lung cancer, these genetic changes are generally somatic, therefore are acquired during life and are present only in certain cells in the lungs. They can be present at different rates according to factors including geographical location, ethnicity, and smoking status. This study characterises the spectrum of molecular and immunological profiles of EBUS-TBNA-diagnosed NSCC samples in the West of Ireland. EBUS-TBNA-diagnosed NSCC reported by the Department for Anatomic Pathology at our institution over a 60-month consecutive period from January 2015 to December 2019 were studied to identify EGFR, ALK, BRAF, ROS1 and PD-L1 status. Over the 60-month period, the percentages of molecular alterations in NSCC were 10.3% EGFR, 6.3% ALK, 2% BRAF, 0% ROS1. In the most recent two years assessed, ALK translocations were identified in 10% (2019) and 11% (2018) of NSCC cases that underwent mutation analysis, which is surprisingly high. In patients with an ALK alteration, 67% had a light or never smoking history. 58.7% squamous carcinoma cases had PD-L1 expression of less than 1%, and 19.5% had PD-L1 expression above 50%. 36.8% adenocarcinomas expressed PD-L1 at less than 1% and 32% expressed PD-L1 at over 50% tumour proportion score. EGFR somatic lung carcinoma mutations were in line with international findings. Sensitising L858R substitutions in exon 21 and in-frame amino acid deletions in exon 19 accounted for 80% of single EGFR mutations. ALK translocation rates of NSCC in the West of Ireland appear notably high for a European population. Squamous carcinoma was more likely to have a low PD-L1 expression, which is unusual given the typical association with smoking and mutation burden.
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