{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:22:57Z","timestamp":1792686177597,"version":"4.5.0"},"reference-count":73,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:p>Tumour protein 63 (p63) is a transcription factor of the <jats:italic>p53<\/jats:italic> gene family, encoded by the <jats:italic>TP63<\/jats:italic> gene located at chromosome 3q28, which regulates the activity of genes involved in growth and development of the ectoderm and derived tissues. p63 protein is normally expressed in the nuclei of the basal cell layer of glandular organs, including breast, in squamous epithelium and in urothelium. p63 immunohistochemical (IHC) staining has several applications in diagnostic breast pathology. It is commonly used to demonstrate myoepithelial cells at the epithelial stromal interface to differentiate benign and <jats:italic>in situ<\/jats:italic> lesions from invasive carcinoma and to characterize and classify papillary lesions including the distinction of breast intraduct papilloma from skin hidradenoma. p63 IHC is also used to identify and profile lesions showing myoepithelial cell and\/or squamous differentiation, e.g. adenomyoepithelioma, salivary gland\u2010like tumours including adenoid cystic carcinoma, and metaplastic breast carcinoma including low\u2010grade adenosquamous carcinoma. This article reviews the applications of p63 IHC in diagnostic breast pathology and outlines a practical approach to the diagnosis and characterization of breast lesions through the identification of normal and abnormal p63 protein expression. The biology of p63, the range of available antibodies with emphasis on staining specificity and sensitivity, and pitfalls in interpretation are also discussed. The <jats:italic>TP63<\/jats:italic> gene in humans, which shows a specific genomic structure, resulting in either TAp63 (p63) isoform or \u0394Np63 (p40) isoform. As illustrated in the figure, both isoforms contain a DNA\u2010binding domain (Orange box) and an oligomerization domain (Grey box). TAp63 contains an N\u2010terminal transactivation (TA) domain (Green box), while \u0394Np63 has an alternative terminus (Yellow box). Antibodies against conventional pan\u2010p63 (TP63) bind to the DNA binding domain common to both isoforms (TAp63 and p40) and does not distinguish between them. Antibodies against TAp63 bind to the N\u2010terminal TA domain, while antibodies specific to \u0394Np63 (p40) bind to the alternative terminus. Each isoform has variant isotypes (\u03b1, \u03b2, \u03b3, \u03b4, and \u03b5).<\/jats:p>","DOI":"10.1111\/his.15101","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T04:17:18Z","timestamp":1701145038000},"page":"723-741","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Tumour 63 protein (p63) in breast pathology: biology, immunohistochemistry, diagnostic applications, and pitfalls"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1681-188X","authenticated-orcid":false,"given":"Rabab","family":"Alkhayyat","sequence":"first","affiliation":[{"name":"Department of Histopathology Nottingham University Hospitals NHS Trust, Nottingham City Hospitals  Nottingham UK"},{"name":"Department of Pathology Salmaniya Medical Complex, Government Hospitals  Manama Kingdom of Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Areeg","family":"Abbas","sequence":"additional","affiliation":[{"name":"Department of Histopathology Nottingham University Hospitals NHS Trust, Nottingham City Hospitals  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8920-5480","authenticated-orcid":false,"given":"Cecily M","family":"Quinn","sequence":"additional","affiliation":[{"name":"Irish National Breast Screening Program, Department of Histopathology St. Vincent's University Hospital, Dublin, School of Medicine, University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5009-5525","authenticated-orcid":false,"given":"Emad A","family":"Rakha","sequence":"additional","affiliation":[{"name":"Department of Histopathology Nottingham University Hospitals NHS Trust, Nottingham City Hospitals  Nottingham UK"},{"name":"Academic Unit for Translational Medical Sciences School of Medicine, University of Nottingham  Nottingham UK"},{"name":"Department of Pathology Hamad General Hospital, Hamad Medical Corporation  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.228015"},{"key":"e_1_2_10_3_1","first-page":"494","article-title":"p63 expression profiles in human normal and tumor tissues","volume":"8","author":"Di Como CJ","year":"2002","journal-title":"Clin. 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