Pathology Outlines

Stains & molecular markers
p63

Author: Nat Pernick, M.D.

Topic Completed: 1 April 2012

Minor changes: 25 September 2020

Copyright: 2002-2021, PathologyOutlines.com, Inc.

PubMed Search: p63 [title]

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Table of Contents

Cite this page: Pernick N p63. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsp63.html. Accessed January 18th, 2021.

Definition / general

Member of p53 gene family at 3q27-29, but does not appear to be a tumor suppressor gene
Myoepithelial marker; others are smooth muscle myosin heavy chains, calponin, p75, P-cadherin, basal cytokeratins (CK 5 / 6), maspin and CD10 (Arch Pathol Lab Med 2011;135:422)

Pathophysiology

Encodes at least 6 different proteins with different biologic functions
Appears to regulate growth and development of epithelial organs (J Biomed Biotechnol 2011;2011:864904), as germline mutations cause ectrodactyly (missing or irregular fingers or toes), ectodermal dysplasia and facial clefts syndrome, also called limb mammary syndrome (hypoplasia / aplasia of mammary glands and nipple)
May be molecular switch for initiation of "epithelial stratification program"
Regulates human keratinocyte proliferation (J Biol Chem 2012;287:5627), olfactory stem cell self renewal and differentiation (Neuron 2011;72:748)
Gene and protein expression may not correlate due to presence of isoforms and post translation modification
Main isoforms are TAp63 and deltaNp63
TAp63 ("full length" p63) activates p53 target genes but deltaNp63 inhibits transcription activation of p53 gene and transactivating isoforms
TAp63 is highly expressed in most benign tumors; negative / weak in most carcinomas but deltaNp63 is negative / weak in most benign tumors and highly expressed in adenoid cystic, mucoepidermoid and myoepithelial carcinomas (Hum Pathol 2005;36:821)

Interpretation

Typically a nuclear stain
Cytoplasmic staining of Z bands of benign and malignant skeletal muscle tumors (Mod Pathol 2011;24:1320)

Uses by pathologists

Rule out invasion in breast tumors by determining presence of myoepithelial cells (Am J Surg Pathol 2001;25:1054)
Confirm diagnosis of prostatic adenocarcinoma (p63−, Am J Surg Pathol 2002;26:1161)
- Triple stain with P504S (AMACR) and CK903 (HMWCK) is recommended (Am J Clin Pathol 2007;127:248)
- Note that partial atrophy may have similar staining as carcinoma (Am J Surg Pathol 2008;32:851)
- Prostate cancer rarely expresses diffuse p63 staining in a nonbasal cell distribution (Am J Surg Pathol 2008;32:461)
Rule out invasion in salivary gland tumors by determining presence of myoepithelial cells
Determine squamous differentiation (p63+) for H&E or cytology cases as part of panel (Am J Clin Pathol 2011;136:81) but p63 rarely stains adenocarcinoma (Am J Surg Pathol 2011;35:15)
Differentiate cutaneous sweat gland / adnexal carcinoma (p63+) from metastatic breast / adenocarcinoma to skin (p63−) as part of panel (Arch Pathol Lab Med 2011;135:975, Mod Pathol 2010;23:713)
Differentiate olfactory neuroblastoma (p63− / calretinin+) from other small round blue cell tumors of sinonasal tract (often p63+ / calretinin−, Am J Surg Pathol 2011;35:1786)
Differentiate renal collecting duct carcinoma (p63− / PAX8+) from upper tract urothelial carcinoma (opposite, Am J Surg Pathol 2010;34:965)
Differentiate high grade prostate cancer (p63−) from infiltrating high grade urothelial cancer (often p63+) as part of panel (Am J Surg Pathol 2007;31:1246)
Associated with poorer prognosis for Merkel cell carcinoma (Mod Pathol 2011;24:1451)
Identifies "false" lymphatic invasion (tumor cells surrounded by D2-40+ / p63+ ducts), which have good prognosis (Mod Pathol 2011;24:502)

Microscopic (histologic) images

Contributed by Andrey Bychkov, M.D., Ph.D.

Solid cell nests

p63+ in many follicles

Correlates with a loss of TTF1

Adenoid cystic carcinoma, solid

Seromucinous hamartoma p63-, no myoepithelial cells, positive internal control

Nephrogenic adenoma (p63-/AMACR+)

Adenocarcinoma (upper, p63-/AMACR+) and benign (lower, p63+/AMACR-)

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

Intraductal papilloma with DCIS immunoprofile

Intraductal papilloma with DCIS, p63

Positive staining - normal

Breast: myoepithelium (Am J Surg Pathol 2001;25:1054), Toker cells
Gynecologic tract: basal and parabasal cells of mature cervical, vaginal and vulval squamous epithelium; cervical reserve cells at transformation zone, immature metaplastic and atrophic cervical squamous epithelium (Adv Anat Pathol 20 09;16:316)
Lung: bronchial reserve cells; metaplastic squamous bronchial epithelium (lower strata)
Prostate basal cells
Skin basal cells
Thymus epithelial cells
Urothelium

Positive staining - disease

Adenoid cystic carcinoma: but not cases with basaloid growth pattern (Mod Pathol 2005;18:1277)
Alveolar rhabdomyosarcoma: p63 cytoplasmic staining of Z-bands of skeletal muscle (Mod Pathol 2011;24:1320)
Bladder: invasive urothelial carcinoma (87%, Am J Surg Pathol 2007;31:673), lymphoepithelioma-like carcinoma (53%, Am J Surg Pathol 2011;35:474)
Bone: aneurysmal bone cyst (63%), chondroblastoma (83%), giant cell reparative granuloma (100%), giant cell tumor (87%), nonossifying fibroma (17%), osteosarcoma (50%), pigmented villonodular synovitis (25%), tenosynovial giant cell tumor (7%, Arch Pathol Lab Med 2011;135:776)
Breast: adenoid cystic carcinoma, collagenous spherulosis (Mod Pathol 2006;19:1351), cylindroma, medullary carcinoma, metaplastic carcinoma (Am J Surg Pathol 2008;32:345), myoepithelioma, nipple adenoma, tubular carcinoma; discontinuous staining in LCIS and DCIS (Am J Surg Pathol 2001;25:1054)
Cervix: epithelioid trophoblastic tumor, lymphoepithelioma-like carcinoma, placental site nodule, spindle cell carcinoma
Heart: cystic tumor of the atrioventricular node (Am J Clin Pathol 2005;123:369)
Jaw: nasolabial cyst (Arch Pathol Lab Med 2011;135:1499), sclerosing odontogenic carcinoma (Am J Surg Pathol 2008;32:1613)
Lymphoma: anaplastic large cell lymphoma (44%) versus 0% for Hodgkin lymphoma (Hum Pathol 2008;39:1505)
Neuroendocrine carcinoma: variable staining, may be focal / weak (Hum Pathol 2008;39:591)
Prostate: basal cell hyperplasia (Hum Pathol 2005;36:480), high grade PIN, adenoid basal cell tumor
Salivary gland: benign or malignant tumors (Hum Pathol 2005;36:821), staining of basal and myoepithelial cells; diffuse staining in oncocytic mucoepidermoid carcinoma (Am J Surg Pathol 2009;33:409)
Sarcomatoid carcinoma (Mod Pathol 2005;18:1471)
Squamous cell carcinoma and squamous component of adenosquamous carcinoma (Hum Pathol 2001;32:479, Cervix; Hum Pathol 2002;33:921, Lung; Am J Clin Pathol 2001;116:823, poorly differentiated/undifferentiated tumors from various sites)
Thymus: hyperplasia and thymoma (Am J Clin Pathol 2009;131:689), thymic carcinoma (Am J Surg Pathol 2009;33:1113)
Thyroid gland: CASTLE, Hashimoto thyroiditis, papillary carcinoma (Hum Pathol 2003;34:764), sclerosing mucoepidermoid carcinoma with eosinophilia, solid cell nests (Mod Pathol 2003;16:43)
Uterus: endometriosis of peritoneal wall (nuclear staining in glandular component), but rectovaginal/abdominal wall endometriosis is p63− (Arch Pathol Lab Med 2007;131:1099), epithelioid trophoblastic tumor (Arch Pathol Lab Med 2006;130:1875)

Negative staining

Anus: anal gland carcinoma (Arch Pathol Lab Med 2007;131:1304), but anal squamous cell carcinoma is usually p63+ (Am J Surg Pathol 2007;31:285)
Breast: normal epithelium, stromal cells, myofibroblasts; may be reduced or occasionally absent in benign apocrine lesions (Am J Surg Pathol 2011;35:202), benign sclerosing lesions (Am J Surg Pathol 2010;34:896) or microglandular adenosis (Am J Surg Pathol 2009;33:496); invasive ductal adenocarcinoma (usually)
Cervix: glassy cell carcinoma
Melanoma (Am J Clin Pathol 2008;130:213)
Mesothelioma
Prostate: adenocarcinoma, nephrogenic adenoma, partial atrophy (Am J Surg Pathol 2008;32:851)
- Rarely, aberrant diffuse expression in prostate carcinoma cells has been seen (Am J Surg Pathol 2008;32:461)
Most soft tissue tumors (Am J Clin Pathol 2011;136:762)
Many glandular tumors are negative / weak