EQAMET

Context and Challenges

MET overexpression is a major predictive biomarker for the efficacy of treatments targeting the MET signaling pathway (capmatinib, tepotinib, antibody-drug conjugates like Teliso-V). However, variability in IHC protocols between laboratories can lead to diagnostic errors, compromising therapeutic selection and the clinical efficacy of targeted treatments.

Main Project Objectives

• Develop standardized samples (reference materials) for MET overexpression in IHC for NSCLC.
• Harmonize MET-IHC analysis protocols (antibody selection, staining techniques, detection systems).
• Implement a standardized interpretation module ("readout") to facilitate the comparison and improvement of practices.

Additional Objectives

• Improve diagnostic accuracy for better selection of patients eligible for anti-MET targeted therapies.
• Promote equity in access to reliable and consistent molecular diagnosis at an international level.

Project Methodology

1. Initial Survey of International Laboratories:
   • Data collection on current practices, technical capacities, and interest from participating laboratories.
   • Selection of 20 representative laboratories based on geographic diversity and expertise.
2. Development of Reference Samples:
   • Creation of synthetic calibrators from an ATCC-validated cell panel, representing different levels of MET expression.
3. External Quality Assessment (EQA) Phase:
   • Distribution of standardized and blinded samples to participating laboratories.
   • Comparative evaluation of results obtained by laboratories using a reference methodology (SP44 clone, Ventana BenchMark Ultra platform).
   • Confirmation using orthogonal techniques (NGS, FISH).
4. Digital Standardized Readout Module:
   • Slide digitization (whole-slide scanner at 40X).
   • Centralized interpretation by an expert committee to assess intensity, localization (membranous/cytoplasmic), and staining homogeneity.
   • Provision of detailed feedback and improvement recommendations to participating laboratories.

Expected Results

• Implementation of a standardized and reliable protocol for MET IHC analysis.
• Significant reduction in inter-laboratory variability.
• Strengthening of diagnostic capacities within participating laboratories.
• Improved therapeutic management for patients with NSCLC.

Long-term Impact

• International standardization of MET-IHC testing for more effective precision medicine.
• Future extension of the program to more laboratories and biomarkers.
• Contribution to global equity in access to innovative targeted therapies.

Involved Institutions

• IHU RespirERA – Clinical and Experimental Pathology Laboratory – Côte d’Azur Biobank – WP3
• IQN Path (International Quality Network for Pathology)