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Stains

p53

Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 5 April 2012, last major update April 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

General
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● 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 (a) DNA repair or (b) to force the cell to undergo apoptosis via activation of bax gene (J Biomed Biotechnol 2011;2011:603925, Wikipedia)
● 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
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● 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
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● 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 (a) genetic changes induced by cellular stress from anoxia or aneuploidy or (b) 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
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● 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)

Micro images
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Bladder: urothelial carcinoma in situ (fig C)


Breast: apocrine DCIS


Breast: DCIS and p53 scoring system


Breast: malignant phyllodes tumor


Breast: medullary carcinoma


Cervix: invasive serous papillary adenocarcinoma


CNS: primary CNS lymphoma (fig C)


Endometrium: endometrial intraepithelial carcinoma

   
Fallopian tube: p53 signatures in tubal intraepithelial neoplasia


Kidney: collecting duct carcinoma (fig D)


Kidney: renal cell carcinoma with rhabdoid features


Skin: atypical fibroxanthoma


Skin: squamous cell carcinoma


Thymus: thymic carcinoma


Thyroid gland: mucus secreting carcinoma with Hurthe cell tumor


Thyroid gland: squamous cell carcinoma arising in a tall cell papillary carcinoma

   
Urethra: clear cell adenocarcinoma

Positive staining - disease
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● 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
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● Cervix: squamous cell carcinoma (usually)
● Uterus: minimal deviation carcinoma

End of Stains > p53

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