p53 staining is a surrogate for TP53 mutation, and both too much and too little are abnormal. Wild-type staining shows nuclei of varying intensity in a scattered, heterogeneous distribution. Aberrant patterns are strong, diffuse nuclear overexpression (usually missense mutation); complete absence of nuclear staining with a positive internal control in stroma or inflammatory cells, the 'null' pattern (usually truncating mutation); and, less commonly, cytoplasmic staining. A null pattern is easily misread as negative and therefore normal, so always check the internal control. Thresholds for 'strong and diffuse' vary by organ and should follow the relevant reporting guidance.
- Heterogeneous, variable nuclear staining is the wild-type pattern.
- Strong, diffuse nuclear staining is aberrant overexpression.
- Complete nuclear absence with a positive internal control is aberrant null, not negative.
- Cytoplasmic staining is an uncommon aberrant pattern worth recognising.
Why it matters
Calling a null pattern 'negative' is a common and consequential reporting error.
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