Stains & molecular markers
p53

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Till Braunschweig, M.D.

Minor changes: 14 September 2021

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PubMed Search: p53 pathology [TI] "free full text" [SB]

Till Braunschweig, M.D.
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Cite this page: Braunschweig T. p53. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsp53.html. Accessed October 18th, 2021.
Definition / general
  • Tumor suppressor gene at 17p13, 53 kDa
  • Mutations are among most commonly detected genetic abnormalities in human neoplasia; however, presence of TP53 mutation is usually not, by itself, specific enough for a diagnosis for malignancy and its absence does not rule out malignancy
Essential features
  • Strong nuclear positivity or complete absence by immunohistochemistry has a strong correlation with the presence of a mutation
  • Low to intermediate expression suggests a nonmutated gene
Pathophysiology
Clinical features
  • Li Fraumeni syndrome: hereditary TP53 mutation causes multiple tumors (J Natl Cancer Inst 1969;43:1365)
  • According to several review publications, incidences of different tumor types are different for women and men (Nat Rev Clin Oncol 2014;11:260, Eur J Hum Genet 2020;28:1379, Cold Spring Harb Perspect Med 2017;7:a026187)
    • Women: almost 100% develop TP53 mutation associated cancer with a risk of 49% by the age of 30
    • Men: 79% develop TP53 mutation associated cancer with a risk of 21% by the age of 30
  • Distribution: breast 28%, soft tissues 14%, brain 13%, adrenocortical 11%, bones 8%, hematological 4%, colorectal 3%, other 19% (gastric, melanoma, lung, pancreas, ovary, bladder, prostate)
  • For children, the spectrum of cancers includes mostly brain tumors as choroid plexus carcinoma, glioma, medulloblastoma and rhabdomyosarcoma (Nat Rev Clin Oncol 2014;11:260)
Interpretation
  • Wildtype (normal) - scattered nuclear staining, mid epithelial (basal sparing)
  • Aberrant (mutational type) → 80% strong and diffuse nuclear staining, complete absence of nuclear staining in all cells, moderate to strong cytoplasmic staining (Int J Gynecol Pathol 2021;40:32)
Uses by pathologists
Prognostic factors
Microscopic (histologic) description
  • Low to intermediate inhomogeneous nuclear expression in up to 50% of wildtype (WT) cases
  • Cutoff values vary in publications, some suggest > 5%, > 10% or > 50% strong positive nuclear stain as positive
  • Cutoff value of > 10% in glioblastoma has low predictive value (Oncotarget 2019;10:6204)
Microscopic (histologic) images

Contributed by Till Braunschweig, M.D.
Barrett esophagus, high grade intraepithelial neoplasia Barrett esophagus, high grade intraepithelial neoplasia

Barrett esophagus, high grade intraepithelial neoplasia, p53+

High grade intraepithelial neoplasia High grade intraepithelial neoplasia

Barrett esophagus, high grade intraepithelial neoplasia, p53 absent

High grade intraepithelial neoplasia High grade intraepithelial neoplasia

Stomach mucosa, high grade intraepithelial neoplasia, p53+


High grade intraepithelial neoplasia High grade intraepithelial neoplasia

Tubular adenoma of the duodenum, high grade intraepithelial neoplasia, p53+

Adenocarcinoma infiltrates Adenocarcinoma infiltrates

Adenocarcinoma in core biopsy of the pancreas, p53+

Intraepithelial carcinoma Intraepithelial carcinoma

Fallopian tube, intraepithelial carcinoma, p53 overexpressed


Serous carcinoma high grade Serous carcinoma high grade

Serous ovarian carcinoma, high grade, p53 overexpressed

Serous carcinoma low grade Serous carcinoma low grade

Serous ovarian carcinoma, low grade, p53 wildtype

Carcinoma in situ Carcinoma in situ

Urothelial carcinoma in situ, p53 absent

Wildtype (normal) staining - normal tissues
  • Virtually all normal tissues should show wildtype p53 expression
Wildtype (normal) staining - disease
Aberrant (mutational type) staining
Molecular / cytogenetics description
Sample pathology report
  • Right ovary, oophorectomy:
    • High grade serous carcinoma (see comment)
    • Comment: Immunohistochemistry for p53 shows strong nuclear positivity in over 80% of tumor cells, consistent with aberrant (mutational type) expression. Controls show appropriate reactivity.
Board review style question #1

Immunohistochemistry of p53 can serve as a distinct marker for the confirmation of high grade neoplastic changes of different tissues. What kind of staining pattern is most common?

  1. Circumferential membranous staining
  2. Cytoplasmic and nuclear staining
  3. Partial membranous staining
  4. Strong cytoplasmic staining
  5. Strong nuclear staining
Board review style answer #1
E. Strong nuclear staining

Comment Here

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