Stains & molecular markers
p53


Topic Completed: 1 April 2012

Minor changes: 3 September 2020

Copyright: 2002-2020, PathologyOutlines.com, Inc.

PubMed Search: p53 [title]

Nat Pernick, M.D.
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Cite this page: Pernick N. p53. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsp53.html. Accessed September 23rd, 2020.
Definition / general
  • Tumor suppressor gene at 17p13, 53 kDa
  • p53 ensures that cells repair any damaged DNA before cell division by inducing cell cycle arrest to allow time for:
  • Mutations are among most commonly detected genetic abnormalities in human neoplasia; however, presence of p53 mutation is usually not, by itself, specific enough for a diagnosis for malignancy, and its absence does not rule out malignancy
  • Li-Fraumeni syndrome: germline heterozygous mutation in p53
Pathophysiology
  • Produces nuclear phosphoprotein involved in transcriptional regulation
  • N terminus amino acids bind (a) TAF's (TATA-binding protein associated factors), which attract other proteins needed to initiate gene expression, as well as (b) MDM2, which inhibits p53 and has the opposite effect as TAF's
  • Wild p53 induces p21 WAF-1, which inhibits cyclin-dependant kinases
  • Wild p53 has half-life of only 20 minutes
  • Inactivated by SV40 T antigen and E1B adenovirus product
    • Sequestered by HPV E6 protein
Interpretation
  • Nuclear stain
  • Usually staining of > 5% of nuclei is considered positive
  • Detected by immunostains only if mutation causes protein stability (although protein may be non-functional) or a physiologic response to:
    • Genetic changes induced by cellular stress from anoxia or aneuploidy
    • Genetic damage to other pathways controlling p53 such as MDM2 or alternative reading frame
  • Staining is associated with aneuploidy, increased S phase fraction and genetic instability
Uses by pathologists
  • Differentiate malignant conditions, which are often p53+ (carcinoma in situ of urothelium and other sites, invasive carcinoma) from reactive and metaplastic conditions which are usually p53- (Am J Surg Pathol 2001;25:1074)
  • May be useful to distinguish uterine serous carcinoma (p53+) from endometrioid carcinoma (usually p53-)
  • May be useful as serum tumor marker (Arch Pathol Lab Med 2011;135:1570)
Microscopic (histologic) images

Contributed by Jijgee Munkhdelger, M.D., Ph.D. and Andrey Bychkov, M.D., Ph.D.

Ovarian serous carcinoma immunoprofile



Case #194

Urethra: clear cell adenocarcinoma



Case #200

Thymic carcinoma



Images hosted on other servers:
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Medullary carcinoma

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Cervix, papillary adenocarcinoma

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Endometrial intraepithelial carcinoma


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Fallopian tube

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Kidney

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Squamous cell carcinoma

Positive staining - normal
Negative staining
  • Cervix: squamous cell carcinoma (usually)
  • Uterus: minimal deviation carcinoma
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