[Quality assurance in dMMR and MSI diagnostics]

Area of Science:

• Oncology
• Pathology
• Molecular Diagnostics

Background:

• Deficient mismatch repair (dMMR) and microsatellite instability (MSI) are critical biomarkers with therapeutic implications across various carcinomas, including colorectal, endometrial, biliary tract, and pancreatic cancers.
• Accurate implementation of dMMR and MSI analyses in pathology institutes necessitates robust quality assurance measures.

Purpose of the Study:

• To evaluate the quality and outcomes of proficiency testing (PT) programs for dMMR and MSI analyses.
• To identify challenges and trends in the implementation of these diagnostic tests in pathology settings.

Main Methods:

• The Pathology Quality Assurance Initiative conducted proficiency tests (PT) for immunohistochemical (IHC) detection of dMMR and molecular pathological analysis of MSI.
• Results from various antibody clones and staining protocols were analyzed.
• Success rates and trends over three years (2018-2020) were assessed.

Main Results:

• Immunohistochemical dMMR testing showed comparable results across different antibody clones, with variations primarily related to staining protocols and interpretation.
• Molecular pathological MSI testing demonstrated a positive quality trend, with success rates increasing from 89% in 2018 to 97% in 2019/2020.
• The choice between commercial and in-house assays did not significantly impact PT outcomes for the selected EQA samples.

Conclusions:

• Proficiency testing programs are essential for maintaining high standards in dMMR and MSI diagnostics.
• Standardization of staining protocols and interpretation guidelines is crucial for improving the reliability of IHC-based dMMR testing.
• The quality of molecular MSI testing is high and improving, with assay choice having minimal impact on PT performance.