Understanding p53 IHC: Wild Type Pattern vs Mutant type pattern

 Historically, p53 IHC has been interpreted as negative or positive based on the percentage of stained tumor cell nuclei using variable cut-offs which range from 5 to 50%.
 More recently, a tripartite interpretation has been suggested, wherein an “overexpressed or no expression (all or nothing)” nuclear staining pattern is highly predictive of underlying TP53 mutation while a normal/wild type pattern is not.
 Of note, rare cases with TP53 mutation rarely show cytoplasmic staining, and, about 5% cases have a wild type pattern

1. WILD TYPE P53 (NORMAL)

The distribution of nuclear staining in a 'wild type' pattern ranges from a few positive cells to almost all cells staining, but with variable intensity.

2. OVEREXPRESSION (ABNORMAL p53)

• Overexpression is defined as strong nuclear staining in at least 80% of tumor cell nuclei (usually 100% tumor cell nuclei, the 80% cut-off accounts for technical artifacts and the rare mosaic pattern, see below).
• Overexpression is the most common (~66%) pattern observed in HGSC, almost certainly signifying an underlying TP53 mutation.

3. COMPLETE ABSENCE OR NULL PATTERN (ABNORMAL)

• Complete absence is defined as no staining in tumor cell nuclei in the presence of
  'wild-type', ie variable, staining in normal background cells (intrinsic control present).
  The interpretation is similar to that of DNA mismatch repair gene protein expression.
• Complete absence is observed in ~25% of HGSC.
• Complete absence is almost certainly indicative of underlying TP53 mutation.

4. CYTOPLASMIC (ABNORMAL)

• Cytoplasmic staining is defined as predominant cytoplasmic staining in the absence of strong nuclear staining in >80% of tumor cell nuclei, i.e. the nuclear staining can be absent or weak and variable.
• The cytoplasmic pattern is seen in ~4% of high-grade serous carcinomas and is associated with underlying TP53 mutation.

Try to answer this MCQ now

https://www.instagram.com/p/CyvxKuSxn0r/?utm_source=ig_web_copy_link&igsh=MzRlODBiNWFlZA==

Correct answer is : Option A -wild type p53. Very rare in high grade serous carcinomas, whereas wild type p53 is seen in low grade serous carcinomas.

REFERENCE ARTICLE

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