Aims Recent clinical trials have shown promising results with drugs targeting the hepatocyte growth factor receptor (c-Met) for advanced non-small cell lung cancers overexpressing c-Met. We assessed reflex testing of c-Met immunohistochemistry (IHC) at diagnosis for NSCLC in the real-world.

Methods We retrospectively collected clinical, pathological and molecular data of cases diagnosed with NSCLC in our institution from January 2021 to June 2023. We performed c-Met IHC (SP44 clone) and scored the expression using a H-score and a three-tier classification.

Results 391 cases with interpretable c-Met IHC staining were included. The median age at diagnosis was 70 years (range 25–89 years) including 234 males (male/female ratio 1:5). 58% of the samples came from surgical resections, 35% from biopsies and 8% from cytological procedures. 52% of cases were classified as c-Met-positive (H-score≥150) and 19% were classified as c-Met^high (≥50%, 3+). 43% of the c-Met^neg presented with lymph node and/or visceral metastases at diagnosis vs 55% for c-Met^high (p=0.042). 23% of the adenocarcinomas showed c-Met^high expression vs 3% for squamous cell carcinomas (p=0.004). 27% of the c-Met^neg cases had a high PD-L1 expression vs 58% of c-Met^high cases (p<0.001). MET ex14 skipping was present in 8% of the c-Met^high cases.

Conclusions Systematic c-Met testing in daily routine for NSCLC patients is feasible, highlighting a potential correlation with clinicopathological and molecular features.