Table 1 Mismatch repair protein immunohistochemistry interpretation pitfalls
From: A practical guide to biomarkers for the evaluation of colorectal cancer
Staining pattern | Possible causes | Next steps |
---|---|---|
Both tumor & internal control show lost/weak expression | Poor fixation or antibody diffusion (if focal); Technical issue with immunohistochemistry | Repeat stain; Stain other block; MSI by PCR |
Tumor weaker than control | Mismatch repair abnormality | Repeat-Call equivocal or lost if still the same; MSI by PCR |
Post neoadjuvant therapy: nucleolar staining, tumor weaker than control, or patchy staining | Post neoadjuvant therapy-related decreased MSH6 (or PMS2) staining | Repeat on pre-treatment biopsy |
Cytoplasmic staining | Technical issue with immunohistochemistry or tissue; Mismatch repair abnormality such as in EPCAM-MSH2 fusion | Repeat; Stain other block; Call lost if cytoplasmic staining only |