Pathology Outlines

Stains
p53

Author: Nat Pernick, M.D.

Topic Completed: 1 April 2012

Revised: 7 March 2019

Copyright: 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: p53 [title]

Page views in 2019: 15,045

Page views in 2020 to date: 4,053

Table of Contents

Cite this page: Pernick N. p53. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsp53.html. Accessed April 3rd, 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:
- DNA repair OR
- To force the cell to undergo apoptosis via activation of bax gene (J Biomed Biotechnol 2011;2011:603925, Wikipedia - p53)
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

Images hosted on PathOut server:

Urethra: clear cell adenocarcinoma

Tthymic carcinoma

Images hosted on other servers:

Ductal carcinoma

Medullary carcinoma

Cervix, papillary adenocarcinoma

CNS lymphoma, Fig.C

Endometrial intraepithelial carcinoma

Fallopian tube

Kidney

Kidney, RCC

Thyroid gland

Squamous cell carcinoma

Positive staining - normal

Various in situ and invasive carcinomas, sarcomas
B-ALL (50%)
Breast: low p53 levels in ADH, higher frequency in comedo DCIS
Colonic adenocarcinoma: increased nuclear staining (Am J Surg Pathol 2002;26:206)
Condyloma
Fallopian tube carcinoma: BRCA+ patients often have p53 signatures in fimbrial epithelium in prophylactic TAHBSO specimens; they represent serous carcinoma in-situ (Curr Opin Obstet Gynecol 2007;19:3, Clin Med Res 2007;5:35, Am J Surg Pathol 2007;31:161)
Urothelial carcinoma in situ: p53+, compare to reactive urothelium, which is p53 negative (Am J Surg Pathol 2001;25:1074)

Negative staining