Introduction

• a protein homologue of p53 that is expressed in poorly differentiated epithelial cells. PMID: 17667171

• plays an important role in regulating epithelial proliferation and differentiation. PMID: 17616998       

• a recently identified homologue of the p53 gene, is mainly expressed by basal and myoepithelial cells in skin. PMID: 17518775

• a member of the p53 family, is an epithelial marker expressed in embryonic ectoderm, breast myoepithelium, prostate, oral epithelium, epidermis, and urothelium. PMID: 17276940

• a transcription factor of the p53 family, is essential for the development of epidermis and its derivatives in vertebrates. PMID: 17264678

• has been shown to be involved in the maintenance of epidermal stem cells and in the stratification of the epidermis. PMID: 17050669

• a novel transcription factor-encoding gene with sequence homology to p53. p63 proteins have epithelial stem-cell regulatory functions and play a critical role in tissue development. PMID: 16979518

• a marker of basal and reserve cells in the female genital tract. PMID: 16912659

• a useful marker for cutaneous spindle cell squamous cell carcinoma. PMID: 16776716

• critical for the development of stratified epithelial tissues such as epidermis, breast, and prostate. PMID: 16406339

• a marker of reserve cells of the bronchus and terminal lobular unit. PMID: 15205681

• a transcription factor that is transcribed into six isoforms, is required for proper development of stratified epithelia, such as the epidermis. PMID: 14757276

• a recently characterized p53 homolog, is a nuclear transcription factor that is expressed in basal cells of multilayered epithelia and myoepithelial cells of the breast. PMID: 12811858

• a p53 homologue that is consistently expressed in basal/stem cells of stratified epithelia and plays a major role in triggering the differentiation of some specific cell lineages. PMID: 12527712

• a p53-related DNA-binding protein that helps regulate differentiation and proliferation in epithelial progenitor cells. PMID: 11727253

• a p53 homologue, is a selective nuclear marker of myoepithelial cells of the human breast. PMID: 11474290

• a prostate basal cell marker and is required for prostate development. PMID: 11106548

Normal Expression

• p63 is strongly expressed in epithelial cells with high clonogenic and proliferative capacity and that stem cells lacking p63 undergo a premature proliferative rundown. PMID: 17482546

• Immunolocalization of p63 proteins, presumably that of full-length p63alpha isoform, was observed in the oocytes of primordial, primary and two-layered secondary follicles. PMID: 17317930

• P63 expression was first observed at E12 when the epidermis was only a simple-layer surface ectoderm. P63 continued to be expressed as the epidermis matured but restricted to the basal layer. In adult trunk epidermis, p63 was expressed in both the hair follicle and the sebaceous glands. PMID: 17244027

• DeltaNp63alpha is the most dominant isoform within human ocular surface epithelia. PMID: 16115622

• Expression of p63 proteins differs between the cell layers in normal oral mucosa, and primary HNSCC has a high expression level of p63 isoforms normally expressed in basal cells. PMID: 15608417

• expressed in the nuclei of myoepithelial cells of normal breast ducts and lobules. PMID: 15489655

• Immunopositive reactions for p63 were observed as early as 10 days after birth and p63 protein was localized to the nuclei of spermatocytes and round spermatids. PMID: 15240943

• p63 is expressed in select epithelial cells at high levels under normal conditions. p63 is highly expressed in embryonic ectoderm and in the nuclei of basal regenerative cells of many epithelial tissues in the adult including skin, breast myoepithelium, oral epithelium, prostate and urothelia. PMID: 15033906

• expressed by basal cells of stratified epithelia and myoepithelial cells. in bone marrow, brain, colon, skeletal muscle, spleen and testis only pro-apoptotic p63 isoforms are expressed, whereas only anti-apoptotic isoforms are present in lung, placenta and salivary gland. In kidney, prostate, skin, thymus, trachea and uterus both variants are present. PMID: 14666701

• Immunostaining for p63 was found in the nucleus of germ cells at E13.5, and continuously observed until E18.5. PMID: 12951416

• a recently characterized p53 homologue, is consistently expressed in myoepithelial cells of the human breast, and is also a sensitive and highly specific marker of myoepithelial cells in canine mammary tissues. PMID: 12824513

• In normal skin, p63 expression was seen in basal/suprabasal cells of the epidermis, outer root sheath and hair matrix cells of the hair follicle, seboblast situated in the outermost layer of sebaceous glands, and outer layer cells of the ductal portion and myoepithelial cells of the secretory portion of the sweat glands. p63 expression was confined to the cells forming a continuous basal rim along the normal epithelial structure. PMID: 12534798

• p63 is expressed in the nuclei of normal human salivary gland myoepithelial and basal duct cells. p63 expression is retained in the modified myoepithelial and basal cells of human salivary gland tumors, which suggests a role for p63 in oncogenesis of these complex tumors. PMID: 12533521

• p63 is a specific myoepithelial cell marker in normal breast tissue and is expressed in a minority of breast carcinomas, being seen only in grade III ductal carcinomas. PMID: 12653579

• TAp63 proteins are located suprabasally in stratified epithelia compared with the N-terminal truncated forms, which are more abundantly expressed in the basal cell layer, indicating a switch in expression of p63 isoforms during normal cellular differentiation. PMID: 12434410

• In normal lung, p63 intensely stained nuclei of bronchial reserve cells but did not stain ciliated cells, alveolar epithelial cells, or nonepithelial cells. The lower strata of squamous metaplastic bronchial epithelium stained positively. All squamous-cell carcinomas stained positively (n = 30). PMID: 12378518

• p63 is consistently expressed in the basal cells of epidermis and cutaneous appendages, including the basal/myoepithelial cells of sweat glands. PMID: 12358808

• in histological sections, p63 was restricted to the nuclei of myoepithelial/basal cells in lobules and ducts of normal breast. PMID: 12203858

• p63 was exclusively expressed in the myoepithelial cells of normal breast, partially expressed in ductal hyperplasia, rarely expressed in carcinoma in situ and not expressed in invasive carcinomas. PMID: 12185332

• p63 expression was restricted to the nucleus, with a nucleoplasmic pattern. We also observed that the expression was restricted to epithelial cells of stratified epithelia, such as skin, esophagus, exocervix, tonsil, and bladder, and to certain subpopulations of basal cells in glandular structures of prostate and breast, as well as in bronchi. PMID: 11839669

• highly expressed in basal cells of the vaginal and cervical epithelium, but not in the uterine epithelium. PMID: 11795399

• In the lower female genital tract, p63 is preferentially expressed in immature cells of squamous lineage and is not linked to cell proliferation. PMID: 11136565

Abnormal Expression

• Immunohistochemical analysis demonstrated the expression of p63 and jag1 in lung tissues of Idiopathic pulmonary fibrosis (IPF). PMID: 17498688

• a member of a gene family also including the p53 tumor suppressor and p73. In contrast to p53, p63 is rarely mutated in human cancers. Rather, gene amplification and dysregulated expression of p63 protein have been observed, particularly in squamous cell carcinomas. PMID: 17477357

• p63 is often over-expressed and amplified in cancer, thus revealing a paradox. PMID: 17426453

• p63 and p73 proteins were overexpressed in 26.3 and 41.0% of EBD carcinomas, respectively. p63 protein expression was more frequent in tumors with vascular invasion (P = 0.002) and distal location (P = 0.04), while p73 expression was more common in cancers with deeper tumor invasion (P = 0.04). PMID: 17385050

• Cytoplasmic expression of p63 is an adverse prognostic factor in patients with adenocarcinoma of the lung. PMID: 16978197

• p63 was expressed in 100% (202/202) of nasopharyngeal carcinoma (NPC) tissues but not in 29 nasopharynx inflammation and 17 non-cancerous nasopharyngeal epidermises on a tissue microarray by immunohistostaining. So p63 might be used as an adjunct diagnostic marker of NPC.  PMID: 16729897

• p63 is consistently expressed in epidermal basal/suprabasal and adnexal basal cells. Most BCCs have higher homogeneous p63 expression than nontumoral epidermis, which is not changed according to histological differentiation subtypes. PMID: 16630179

• p63 antigen may be a useful marker of myoepithelial cells in salivary glands neoplasms. PMID: 16256413

• p63 and p73 expression is retained in both benign and malignant salivary gland tumors with basaloid or myoepithelial differentiation. Hence, p63 seems to be a more specific marker of myoepithelial differentiation than p73. PMID: 16021638

• In conjunctival intraepithelial neoplasia and squamous cell carcinoma of the conjunctiva, p63 is preferentially expressed in the immature dysplastic epithelial cells. PMID: 16021499

• p63 is an especially useful marker of myoepithelial cells with naked nuclei in epithelial-myoepithelial carcinoma (EMC). PMID: 15959915

• p63 expression in desmoplastic ameloblastomas was significantly higher than in acanthomatous and granular cell ameloblastomas, and ameloblastic carcinomas showed higher p63 expression than metastasizing ameloblastomas. PMID: 15752257

• p63 is expressed in oral carcinomas and dysplasias, as determined by immunohistochemical staining with a primary antibody to all isotypes. PMID: 15583543

• p63 expression is consistently expressed in squamous cell carcinoma in the lung, but is also expressed in a subset of adenocarcinomas and large cell carcinomas. Pulmonary neuroendocrine tumors also show p63 staining in some instances, particularly in higher-grade tumors, and the majority of small cell carcinomas are p63-positive. PMID: 15551738

• Immunoreactivity for p63 was detected in 96.9% (63/65) esophageal squamous cell carcinomas. PMID: 15254760

• P63 is strongly expressed in basal cell adenoma of parotid origin, and in adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA). PMID: 15153875

• Primary sclerosing mucoepidermoid carcinomas with eosinophilia (SMECE) of the thyroid gland (SMECE) stain strongly positive for p63. PMID: 15001991

• P63 as detected using immunohistochemistry is present in squamous cell carcinomas of the oral cavity (OSCC). PMID: 14997391

• p63 is commonly expressed in papillary thyroid carcinoma and in Hashimoto's thyroiditis. PMID: 14506636

• p63 can be used as a marker of basal cells and in vitro typing cell cultures of prostate cancer (CaP). PMID: 12553000

• DeltaNp63 is the major isotype expressed in epithelia and tumors of the esophagus. Elevated expression of p63 is probably an early event in esophageal squamous cell carcinomas, which may play a significant role in the development of the disease. PMID: 12447998

• Analysis of squamous cell carcinomas shows DeltaNp63alpha to be the most widely expressed isoform, compatible with a role for this protein in promoting neoplastic cell growth in these tissues. DeltaNp63 protein expression is also restricted to basal cells in breast and prostate, whilst TAp63 isoforms are more widely expressed in these tissues as well as in tumours at these sites. TAp63, but not DeltaNp63 or p63alpha, is detected in normal colon and in colon carcinoma. TAp63 proteins are also expressed in the nuclei of a sub-population of lymphoid cells and in most malignant lymphomas, whereas DeltaNp63 proteins are not expressed. PMID: 12434410

• positive immunostaining for both p63 and CK5/6 in poorly differentiated metastatic carcinomas is highly predictive of a primary tumor of squamous epithelial origin. PMID: 11764070

• altered expression of p63 is a frequent event in bladder carcinogenesis and might contribute to the progression of bladder tumors, possibly via the mechanism(s) distinct from the p53 pathway. PMID: 10910040

• Over-expression of p63 alpha, and in particular the delta N form, was frequently seen in carcinomas. PMID: 10897041

Function

• play an important role in the development of skin tumors and work synergetically in malignant skin tumors. PMID: 17497299

• p63 is able to trigger gonocyte apoptosis in control testis but is not necessarily required in their radio-induced apoptosis. PMID: 17148261

• p63 is required for both the proliferative and differentiation potential of developmentally mature keratinocytes. PMID: 17114587

• p63 appears as an important regulator of germ cell development. PMID: 16998800

• an important role of p63 in the control of ovarian epithelium behavior. The p63 may be involved in the development of benign and malignant epithelial ovarian tumors. PMID: 16445626

• p63 is essential for developmental neuronal death, likely functioning both on its own, and as an obligate proapoptotic partner for p53. PMID: 16337913

• p63, particularly its splice variant DeltaNp73L, is involved in the neoplastic transformation of salivary glands. PMID: 16273188

• p63 may be involved in the early stage of the remodeling process of the psoriatic epidermis as well as in the elongation of the rete ridges. PMID: 15863843

• p63 may be involved in the regulation of primordial germ cells (PGC) development by controlling the gene expression required for their migration and colonization to the gonads. PMID: 15585950

• aberrant p63 expression plays a role not only in malignant tumors but also in benign skin diseases that show hyperproliferation of epidermal cells in vivo. PMID: 15248062

• p63 plays a critical role in the development of normal esophageal and tracheobronchial epithelia and appears to control the commitment of early stem cells into basal cell progeny and the maintenance of basal cells. PMID: 15189821

• specific p63 isoforms were associated with human oral squamous cell carcinogenesis.  PMID: 15183414

• p63 plays a dual role: initiating epithelial stratification during development and maintaining proliferative potential of basal keratinocytes in mature epidermis. PMID: 14729569

• p63 plays critical roles in tumor progression and biochemical terminal differentiation of urothelial neoplasms. PMID: 14654529

• both p73 and p63 may be involved in the development of human buccal squamous-cell carcinoma, perhaps in concert with p53. PMID: 12969350

• DeltaNp63 could be involved in the control of physiologic processes, such as cell proliferation and migration, related to epidermal repair during healing of normal skin in humans. PMID: 11604626

Diagnostic & Therapeutic Value

• p63 expression is associated with a worse prognosis in patients with Merkel cell carcinoma (MCC) and represents a new independent marker of clinical evolution. PMID: 17599745

• p63 immunostain is a highly specific and useful tool in the diagnosis of carcinomas of the anal canal. PMID: 17255774

• p63 is a useful immunocytochemical marker for differentiating primary glandular pathology from HSIL in cervicovaginal specimens. PMID: 17173320

• p63 expression is a disadvantageous factor for prognosis in this subgroup of B-cell lymphomas. PMID: 16918993

• p63 can be useful in the differential diagnosis between cholangiocarcinomas (CC) and hepatocellular carcinomas (HCC) in biopsy samples. PMID: 16872309

• may be used as an adjunct marker in the diagnosis of metaplastic carcinoma. PMID: 16484002

• although a reduced expression of p63 is infrequent, it has a prognostic impact upon patients with esophageal squamous cell carcinoma (ESCC). PMID: 16391849

• p63 expression may be useful to identify cases of oral squamous cell carcinoma with more aggressive and invasive phenotype providing novel diagnostic and prognostic information on individual patient survival with oral cancers. PMID: 15754296

• p63 immunostaining constitutes a specific and accurate means of distinguishing adenoid cystic carcinoma from basaloid squamous cell carcinoma. PMID: 15529180

• a highly sensitive and specific marker of metaplastic carcinoma. PMID: 15489655

• useful in the distinction of epithelioid trophoblastic and placental site trophoblastic tumors by profiling trophoblastic subpopulations. PMID: 15316317

• p63 is a sensitive and specific myoepithelial marker, and may be included in immunohistochemical panels aiming to identify myoepithelial cells in problematic breast lesions. PMID: 15024707

• a sensitive and specific myoepithelial marker and may be included in immunohistochemical panels aiming at identifying myoepithelial cells in problematic breast lesions. PMID: 14758723

• there is early and frequent genomic amplification of p63 in the development of squamous carcinoma of the lung and that patients with NSCLC showing amplification and overexpression of p63 have prolonged survival. PMID: 14612504

• P63 expression was detected in 51/53 (96.2%) transitional cell carcinoma (TCC) of the bladder (TCCs), showing decreased expression in high-stage (pT1 and pT2 100%; pT3 90.9%) and poorly differentiated (G1 and G2 100%; G3 92%) tumors. All renal-cell carcinoma (RCCs) were negative for p63. P63 proved to be a helpful tool, even in poorly differentiated and undifferentiated renal malignancies, to distinguish TCC from RCC. PMID: 12871991

• p63 and TTF-1 appear to be useful for differentiating small cell lung carcinoma (SCLC) from lung poorly differentiated squamous cell carcinoma (PDSCC) in formalin-fixed and alcohol-fixed, formalin-postfixed material. PMID: 12760288

• p63 expression may be a marker of basal/progenitor cells in tumors of epidermis and epidermal appendages, and may be a diagnostic marker of these tumors. PMID: 12534798

• p63 antibodies may help in distinguishing solid cell nests from their mimics. PMID: 12527712

• p63 may represent a myoepithelial marker that can complement or replace SMM-HC and/or calponin in the analysis of difficult breast lesions. PMID: 12502930

• p63 staining is at least as sensitive and specific for the identification of basal cells in diagnostic prostate specimens as is high molecular weight cytokeratin staining. PMID: 12481011

• abnormal expression of p63 may be involved in the early phases of laryngeal tumorigenesis irrespective of p53 gene status and that TA-p63 mRNA down-regulation, but not p63 IR, may be clinically relevant in patients with LSCC. PMID: 12379767

• The identification of p63 as a keratinocyte stem cell marker will be of practical importance for the clinical application of epithelial cultures in cell therapy as well as for studies on epithelial tumorigenesis. PMID: 11248048

Review Articles

• p63 transcriptional regulation of epithelial integrity and cancer. PMID: 17297296

• p63, cell adhesion and survival. PMID: 17297292

• One, two, three--p53, p63, p73 and chemosensitivity. PMID: 17287142

• The roles of p63 in cancer. PMID: 17264676

• p63-associated disorders. PMID: 17224651

• p63: a new link between senescence and aging. PMID: 16434880

• Neurodevelopment on route p63. PMID: 16337905

• p63 and epithelial appendage development. PMID: 15606495

• From p63 to p53 across p73. PMID: 11223031

• Structure, function and regulation of p63 and p73. PMID: 10637429

Applications

Immunocytochemistry (ICC)

• Immunostaining for the myoepithelial cell marker p63 has been shown to be useful to separate noninvasive from invasive breast lesions in histologic examination. PMID: 17580273

Immuno-Electron Microscopy (IEM)

• we have produced a polyclonal antibody against the purified human p63 protein to reassess the subcellular distribution of p63 by confocal immunofluorescence, immunoelectron microscopy, and cell fractionation. PMID: 7673362

Immunofluorescence (IF)

• Immunofluorescence reveals p63 expression in skin, oral epithelium, tongue, kidney, and trachea, but not in liver, large intestine, testis, skeletal muscle, or heart. PMID: 11532371

Immunohistochemistry (IHC)

• Expression of p63 protein was evaluated by immunofluorescence and immunohistochemistry in normal male human urogenital tract tissues. PMID: 17070310

• p63 expression at the microanatomic detail was examined by immunohistochemistry using a monoclonal antibody (clone 4A4), while distinction of p63 isoforms was analyzed by Western blotting and reverse transcription-polymerase chain reaction using isoform-specific primers. PMID: 16082248

• A total of 123 cases of odontogenic cysts, distributed as follows: 30 follicular (FC), 35 radicular (RC), 53 keratocysts, 1 glandular odontogenic and 4 calcifying odontogenic cysts, were analysed by immunohistochemistry for expression of p63, a component of p53 protein family. PMID: 16053892

• Immunohistochemistry with the p63 antibody (clone 4A4) was performed in formalin-fixed paraffin-embedded samples of hydropic abortion (n=10), partial hydatidiform mole (n=12), complete hydatidiform mole (n=12) and choriocarcinoma (n=5). PMID: 16026831

• Immunohistochemical p63 staining was compared for samples from 90 male patients with buccal epithelial dysplasias and 15 healthy individuals with normal buccal mucosa and 15 subjects with reactive epithelial hyperplasia of the oral mucosa secondary to traumatic insult. PMID: 15752259

• Immunohistochemical analysis for p63 was performed on formalin-fixed, paraffin-embedded archival tissue from 20 benign adnexal tumors, 10 malignant adnexal tumors and 14 adenocarcinomas metastatic to the skin. PMID: 15389254

• Four-micrometer sections from 88 routinely fixed and processed archival thyroidectomy specimens were pretreated with citric acid pH 6.0 for antigen retrieval, then incubated overnight with anti-p63 monoclonal antibody 4A4. Slides were stained with a streptavidin-biotin kit and diaminobenzidine as chromogen and were counterstained with hematoxylin. PMID: 15116328

• Immunostaining for p63 expression was performed on 10 pairs of pterygium and normal conjunctiva using a monoclonal antibody directed against human p63. PMID: 14701960

• Immunohistochemical analysis of p63 protein expression was performed in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch squamous cell carcinogenesis. PMID: 14628890

• We performed immunohistochemistry with an anti-p63 antibody on specimens from radical prostatectomies, prostate needle biopsies, and metastatic prostate adenocarcinoma. PMID: 11597556