# MET Expression in Upper Gastrointestinal Adenocarcinoma: Prevalence, Prognostic Impact, and Implications for Anti-MET Antibody-Drug Conjugate Therapy

Article · Bedau T, Zander T, Anton Schlößer H, Alakus H, Mustafov O, Büttner R, Bruns C, Quaas A

- Archive id: doi:10.1002/ijc.70634
- Published: 2026-07-02
- Venue: International journal of cancer
- DOI: https://doi.org/10.1002/ijc.70634
- PMID: 42394136
- PMCID: PMC13595460
- Citations: 0
- Source URL: https://doi.org/10.1002/ijc.70634
- PDF: https://europepmc.org/articles/PMC13595460/pdf
- Provenance: europepmc

## Abstract

MET is an actionable receptor tyrosine kinase, and MET-directed antibody-drug conjugates (ADCs) have recently entered clinical practice with FDA approval in non-small cell lung cancer and are now being evaluated across gastrointestinal malignancies, with patient selection based on MET immunohistochemistry (IHC) 3+ membranous staining at varying percentage thresholds. However, robust real-world data on MET protein expression and clinically relevant ADC-aligned thresholds in upper GI adenocarcinomas remain limited. We profiled 1532 upper GI adenocarcinomas using the clinically validated VENTANA MET (SP44) IHC assay. MET was stratified by (i) 3+ membranous staining fractions (any, ≥ 10%, ≥ 50%) reflecting contemporary ADC eligibility concepts and (ii) H-score (0-300; high ≥ 150). Overall survival analyses and multivariable Cox regression analyses were performed. High MET expression was uncommon (H-score ≥ 150: 2.3%; any 3+: 1.6%; ≥ 10% 3+: 1.3%; ≥ 50% 3+: 1.0%) and enriched in advanced T stage. MET IHC strongly predicted MET amplification (H-score ≥ 150: 63.6% amplified vs. 2.4% in negatives; any 3+: 75.0% vs. 2.6%; all p \< 0.001). Any MET 3+ staining was independently associated with inferior overall survival (adjusted HR 2.22, 95% CI 1.29-3.83). Most MET 3+ tumors lacked concurrent HER2 positivity, Claudin-18.2 expression, or dMMR/MSI. In the largest real-world cohort to date, MET overexpression identifies a rare, biologically aggressive subset with poor outcomes. By applying the latest MET-ADC-relevant IHC criteria (including the ≥ 10% 3+ threshold), this study provides clinically translatable prevalence estimates and supports standardized MET testing to inform prospective MET-directed ADC trials in upper GI adenocarcinoma.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Cancer Immunotherapy](https://space-kitty.com/topics/cancer-immunotherapy)

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