Scoring Reliability of c-Met Immunohistochemical Assays in Lung Adenocarcinoma

c-Met overexpression may identify patients who benefit from MET inhibitor therapy. However, concordance among c-Met immunohistochemistry (IHC) assays and scoring system reliability remain unclear. We retrospectively analyzed 150 lung adenocarcinoma specimens (from December 2018 to March 2023) using 5 c-Met IHC assays (SP44_R, SP44_Z, D1C2, LBP4-C-MET, and 811B7F4), scored by H-score, clinical score, 2-tier H-score (H-score ≥150 as positive) and 2-tier clinical score (clinical score 2+/3+ as positive). Next-generation sequencing for MET alterations was performed on 107 samples. H-scores of the 5 assays showed excellent interassay reliability (intraclass correlation coefficient = 0.953). Compared with SP44_R, which is the most frequently used antibody in the clinical trial, SP44_Z had the highest correlation with it (ρ = 0.851), followed by D1C2 (ρ = 0.818), LBP4-C-MET (ρ = 0.786), and 811B7F4 (ρ = 0.737). Among the 5 assays, Kendall W for the clinical score was 0.697; Fleiss κ for the 2-tier H-score was 0.51 and for the 2-tier clinical score was 0.494. In comparison with the clinical score 3+ of SP44_R, SP44_Z and 811B7F4 showed moderate reliability (κ = 0.483), LBP4-C-MET (κ = 0.459), and D1C2 (κ = 0.234). Nearly perfect agreement existed between the 2-tier H-score and clinical score (κ range: 0.944-0.986). In contrast, correlation analysis between H-scores across all assays and RNA expression levels revealed a weak association (ρ = 0.159-0.349). Five c-Met IHC assays demonstrated moderate-to-strong concordance in detecting c-Met overexpression. SP44_R, SP44_Z, LBP4-C-MET, and 811B7F4 performed reliably, although D1C2 was less consistent for clinical score 3+. A clinical score of 2+/3+ or an H-score of ≥150 is associated with high diagnostic consistency, supporting multiple validated IHC assays for c-Met evaluation in lung adenocarcinoma.