MET exon 14 skipping mutation (METex14) is a key oncogenic driver in 2% of non-small cell lung carcinoma (NSCLC) and is enriched in sarcomatoid carcinoma (SAC). However, the prevalence and significance of METex14 NSCLC in the Australian population is not known. We evaluated the incidence, clinical, molecular, and histopathological features of METex14 and SAC cases in an Australian tertiary referral centre. We retrospectively analysed clinical, molecular, histopathological, and immunohistochemical data of NSCLC cases undergoing DNA and/or RNA fusion panel next-generation sequencing (NGS) between 1 July 2021 and 15 May 2024. Among 1267 NSCLC, 880 (69%) cases had DNA NGS only, 359 (28%) cases had both DNA NGS and RNA fusion panel, and 28 (2%) cases had RNA fusion panel only. Overall, 29 (2.3%) cases had METex14, 14 (1.1%) had MET amplification, and 10 (0.8%) had MET R988C. Of the 29 METex14 patients, 15 (52%) were women and 14 (48%) were men. METex14 patients were older than those who were MET wild-type, or with EGFR or KRAS mutations (median age 76 vs 71, 69, and 71, respectively) and were less likely to be smokers than KRAS-mutated cases (58% vs 92%, p<0.0001). Most METex14 cases were adenocarcinomas (76%), with 14% classified as SAC. Programmed death-ligand 1 (PD-L1) expression was higher in METex14 than in EGFR-mutated cases. Median survival for METex14 patients was 26 months (stage I), not reached (stage II), 8 months (stage III), and 3.5 months (stage IV). Among 28 SAC cases, 57% harboured oncogenic mutations, including KRAS (18%), METex14 (14%), BRAF V600E (7%), and EGFR exon 19 deletion (4%). SAC exhibited significantly higher PD-L1 expression (mean tumour proportion score 71 vs 30, p<0.0001) and a greater proportion of high PD-L1 expressors (82% vs 30%, p<0.0001) than other NSCLC subtypes. Stage IV SAC patients had a median survival of only 2 months. In summary, in our cohort of NSCLC, METex14 mutation was found in 2% of cases using DNA NGS alone and up to 3% when both DNA NGS and RNA fusion panel testing were employed. METex14 mutations were more common in elderly patients, with an equal gender distribution and a high proportion of non-smokers. While most cases were adenocarcinomas, SAC was enriched for METex14. SAC was an aggressive NSCLC subtype, with KRAS and METex14 as the most common driver mutations. Given the high prevalence of PD-L1 expression in SAC, further research on immunotherapy efficacy in this group is warranted.
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