Stains & molecular markers
p53
Copyright: 2002-2020, PathologyOutlines.com, Inc.
PubMed Search: p53 [title]
p53
Author: Nat Pernick, M.D.
Topic Completed: 1 April 2012
Minor changes: 25 September 2020
Copyright: 2002-2020, PathologyOutlines.com, Inc.
PubMed Search: p53 [title]
Table of Contents
Definition / general | Pathophysiology | Interpretation | Uses by pathologists | Microscopic (histologic) images | Positive staining - normal | Negative stainingCite this page: Pernick N. p53. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsp53.html. Accessed December 5th, 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
Contributed by Jijgee Munkhdelger, M.D., Ph.D., Andrey Bychkov, M.D., Ph.D. and Semir Vranic, M.D., Ph.D.
Ovarian serous carcinoma immunoprofile
Medullary carcinoma
Cases #194 and #200
Urethra: clear cell adenocarcinoma
Thymic carcinoma
Images hosted on other servers:
Cervix, papillary adenocarcinoma
Endometrial intraepithelial carcinoma
Fallopian tube
Kidney
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
- Cervix: squamous cell carcinoma (usually)
- Uterus: minimal deviation carcinoma
