Stains & CD markers
p63
Copyright: 2002-2022, PathologyOutlines.com, Inc.
PubMed Search: p63 [title]
p63
Author: Nat Pernick, M.D.
Last author update: 1 April 2012
Last staff update: 14 April 2022
Copyright: 2002-2022, PathologyOutlines.com, Inc.
PubMed Search: p63 [title]
Table of Contents
Definition / general | Pathophysiology | Interpretation | Uses by pathologists | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative stainingCite this page: Pernick N p63. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsp63.html. Accessed May 18th, 2022.
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
