p53 immunohistochemistry is an accurate surrogate for TP53 mutational analysis in endometrial carcinoma biopsies

J Pathol. 2020 Mar;250(3):336-345. doi: 10.1002/path.5375. Epub 2020 Jan 29.


TP53 mutations are considered a surrogate biomarker of the serous-like 'copy number high' molecular subtype of endometrial carcinoma (EC). In ovarian carcinoma, p53 immunohistochemistry (IHC) accurately reflects mutational status with almost 100% specificity but its performance in EC has not been established. This study tested whether p53 IHC reliably predicts TP53 mutations identified by next-generation sequencing (NGS) in EC biopsy samples for all ECs and as part of a molecular classification algorithm after exclusion of cases harbouring mismatch repair defects (MMRd) or pathogenic DNA polymerase epsilon exonuclease domain mutations (POLEmut). A secondary aim assessed inter-laboratory variability in p53 IHC. From a total of 207 cases from five centres (37-49 cases per centre), p53 IHC carried out at a central reference laboratory was compared with local IHC (n = 164) and curated tagged-amplicon NGS TP53 sequencing results (n = 177). Following consensus review, local and central p53 IHC results were concordant in 156/164 (95.1%) tumours. Discordant results were attributable to both interpretive and technical differences in staining between the local and central laboratories. When results were considered as any mutant pattern versus wild-type pattern staining, however, there was disagreement between local and central review in only one case. The concordance between p53 IHC and TP53 mutation was 155/168 (92.3%) overall, and 117/123 (95.1%) after excluding MMRd and POLEmut EC. Three (3/6) discordant results were in serous carcinomas with complete absence of p53 staining but no detectable TP53 mutation. Subclonal mutant p53 IHC expression was observed in 9/177 (5.1%) cases, of which four were either MMRd or POLEmut. Mutant pattern p53 IHC was observed in 63/63 (100%) serous carcinomas that were MMR-proficient/POLE exonuclease domain wild-type. Optimised p53 IHC performs well as a surrogate test for TP53 mutation in EC biopsies, demonstrates excellent inter-laboratory reproducibility, and has high clinical utility for molecular classification algorithms in EC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Keywords: TP53; The Cancer Genome Atlas; endometrial carcinoma; molecular classification; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Endometrioid / genetics
  • Carcinoma, Endometrioid / metabolism*
  • Carcinoma, Endometrioid / pathology
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / metabolism*
  • Cystadenocarcinoma, Serous / pathology
  • DNA Mutational Analysis
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / pathology
  • Female
  • Humans
  • Immunohistochemistry*
  • Mutation*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*


  • Tumor Suppressor Protein p53