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