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Concordance of DNA Mismatch Repair Proteins in Primary Esophagogastric Adenocarcinomas and Distant Metastases

Author(s): Juliana Knief, Ekaterina Petrova, Pamela Lazar-Karsten, Ulrich Wellner, Richard Hummel, Christoph Thorns

Introduction: Mismatch repair proteins (MMR) are commonly evaluated during routine workup in a variety of epithelial tumours. The incidence of deficiency in upper gastrointestinal carcinomas varies between 10-20%. In colorectal adenocarcinomas, mismatch repair protein expression shows high concordance between primary tumours and metastases but up to date no such data is available for esophagogastric adenocarcinomas.

Materials and Methods: 41 primary adenocarcinomas of the esophagogastric junction and matched distant metastases were analysed using immunohistochemistry with antibodies against MLH1 and MSH2. DNA mismatch repair status (deficient or proficient) was determined and correlated with clinical outcome.

Results: Concordance of mismatch repair status between primary tumours and metastases was relatively low (52.5%). No correlation with clinical features and no impact on overall survival could be demonstrated although mismatch repair protein proficiency showed a trend towards prolonged survival (p=0.097).

Conclusion: In contrast to colorectal carcinomas, concordance of MMR in esophagogastric carcinomas is low. Therefore, clinicians and pathologists alike should exercise caution when choosing tissue for immunohistochemical evaluation as these results might influence therapeutic procedures (i.e. the application of immune checkpoint inhibitors).

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