Identification of a Basal/Reserve Cell Immunophenotype in Benign and Neoplastic Endometrium: A Study with the p53 Homologue p63

O'Connell, Jerome T.; Mutter, George L.; Čviko, Aida; Nucci, Marisa R.; Quade, Bradley J.; Kozakewich, Harry P.; Neffen, Eduardo; Sun, Deqin; Yang, Annie; McKeon, Frank; Crum, Christopher P.

doi:10.1006/gyno.2000.6026

Cited by 65 publications

(58 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[13][14][15][16][17][18][19][20] Conversely, renal and Barrett's metaplastic epithelium and associated adenocarcinomas, which lack the capacity for squamous differentiation, are consistently p63-negative. 16,23 Adenoid cystic carcinomas, which lack the capacity for squamous differentiation but are p63-positive, appear to be one exception to this principle.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11][12] Expression has also been established in a variety of neoplasms, including squamous, urothelial, endometrial, and papillary thyroid carcinomas and thymomas. [13][14][15][16][17][18][19][20] p63 expression in salivary gland and salivary neoplasms has also been investigated. Benign myoepithelial cells of salivary gland, like those of normal breast and prostate epithelium, express p63.…”

mentioning

confidence: 99%

See 1 more Smart Citation

p63 Immunohistochemistry in the distinction of adenoid cystic carcinoma from basaloid squamous cell carcinoma

et al. 2005

View full text Add to dashboard Cite

Morphologic distinction of high-grade adenoid cystic carcinoma from basaloid squamous cell carcinoma can be difficult. Equivocal diagnoses can mislead treatment. We have investigated the possibility that immunohistochemical staining for the presence of p63, a novel epithelial stem-cell regulatory protein, could be a useful means of distinguishing these two neoplasms. Archival, routinely processed slides were subjected to citrate-based antigen retrieval, exposure to anti-p63 monoclonal 4A4, and developed with a streptavidinbiotin kit and diaminobenzidine as chromogen. p63 was detected in 100% of the adenoid cystic carcinomas (n ¼ 14) and 100% of basaloid squamous cell carcinomas (n ¼ 16). Basaloid squamous cell carcinomas consistently displayed diffuse p63 positivity, with staining of nearly 100% of tumor cells. In contrast, adenoid cystic carcinoma displayed a consistently compartmentalized pattern within tumor nests. Compartmentalization was manifested in two patterns: (1) selective staining of a single peripheral layer of p63-positive cells surrounding centrally located tumor cells that were p63-negative and (2) tumor nests consisting of multiple contiguous glandular/cribriform-like units of p63-positive cells surrounding or interspersed with p63-negative cells. p63 immunostaining constitutes a specific and accurate means of distinguishing adenoid cystic carcinoma from basaloid squamous cell carcinoma. p63 positivity in adenoid cystic carcinoma appears to be homologous to that seen in the basal and/or myoepithelial compartments of salivary gland and other epithelia, and may signify a stem-cell-like role for these peripheral cells. Diffuse p63 positivity in basaloid squamous cell carcinoma suggests dysregulation of p63-positive stem cells in poorly differentiated squamous carcinoma.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

p63 Immunohistochemistry in the distinction of adenoid cystic carcinoma from basaloid squamous cell carcinoma

et al. 2005

View full text Add to dashboard Cite

show abstract

“…The ⌬Np63 isoforms are believed to function as a dominantnegative factor that inhibits the transactivation of p53 and TAp63 proteins. [27][28][29][30][31][32][33] The differential role and function of Expression of p63 isoforms in benign tumors. WT indicates Warthin's tumor; ME, myoepithelioma.…”

mentioning

confidence: 99%

Expression and Regulation of the ΔN and TAp63 Isoforms in Salivary Gland Tumorigenesis

Mitani

Weber

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

The TP63 gene, a TP53 homologue, encodes for two main isoforms by different promoters: one retains (TA) and the other lacks (⌬N) the transactivation domain. p63 plays a critical role in the maintenance of basal and myoepithelial cells in ectodermally derived tissues and is implicated in tumorigenesis of several neoplastic entities. However, the biological and regulatory roles of these isoforms in salivary gland tumorigenesis remain unknown. Our results show a reciprocal expression between TA and ⌬N isoforms in both benign and malignant salivary tumors. The most dominantly expressed were the ⌬N isoforms, whereas the TA isoforms showed generally low levels of expression, except in a few tumors. High ⌬Np63 expression characterized tumors with aggressive behavior, whereas tumors with high TAp63 expression were significantly smaller and less aggressive. In salivary gland cells, high expression of ⌬Np63 led to enhanced cell migration and invasion and suppression of cell senescence independent of TAp63 and/or TP53 gene status. We conclude the following: i) overexpression of ⌬Np63 contributes to salivary tumorigenesis, ii) ⌬Np63 plays a dominant negative effect on the TA isoform in the modulation of cell migration and invasion, and iii) the ⌬N isoform plays an oncogenic role and may represent an attractive target for therapeutic intervention in patients with salivary carcinomas.

show abstract

“…P63+ komórki rozsiane w zdrowym endometrium to prawdopodobnie podstawne komórki rezerwowe lub komórki macierzyste potencjalnie zdolne ulegać różnym typom metaplazji. W jajnikach i nabłonku jajowodów komórki p63+ to prawdopodobnie ogniska nabłonka przejściowego, często obserwowane w tych narządach [43,45].…”

Section: Ekspresja I Przydatność Diagnostyczna P63 W Nowotworach Skóryunclassified

“…W badaniu immunohistochemicznym widoczny jest charakterystyczny wzór świecenia p63 w obrębie komórek rezerwowych, który może być przydatny w różnicowaniu hiperplazji mikrogruczołowej szyjki macicy z rakiem endometrialnym [47]. Ograniczeniem metody jest sporadyczna obecność komórek p63+ w ogniskach metaplastycznych nowotworu [45].…”

Section: Ekspresja I Przydatność Diagnostyczna P63 W Nowotworach Skóryunclassified

The role of p63 proteins in tumorigenesis and the significance of their expression in the diagnosis of skin and female genital tract neoplasms

Wysocka-Dubielecka¹,

Majewski²,

Loza³

2015

View full text Add to dashboard Cite

STRESZCZENIEProteiny p63 są homologami białka p53 i razem z p73 tworzą rodzinę białek p53, która obejmuje czynniki transkrypcyjne regulujące metabolizm, proliferację, różnicowanie, starzenie się i śmierć komórki. Białko p63 odgrywa znaczącą rolę w rozwoju i funkcjonowaniu naskórka i innych nabłonków płaskich oraz ma znaczenie w procesie kancerogenezy. p63 występuje w wielu izoformach zaliczanych do 2 głównych grup: TAp63 oraz ΔNp63. TAp63 są produkowane w bardzo małych stężeniach (z wyjątkiem oocytów). ΔNp63 stanowią dominującą izoformę i wystę-pują głównie w podstawnych komórkach nabłonkowych skóry, przydatków, piersi, prostaty i układu moczowego. W przeciwieństwie do TAp63, formy ΔN uznaje się za onkoproteiny. W żeńskim układzie rozrodczym p63 może mieć duże znaczenie w diagnostyce problematycznych raków, gdy rozpoznanie decyduje o dalszym postępowaniu terapeutycznym. Białka p63 biorą też udział w aktywacji transkrypcji późnych genów HPV podczas proliferacji i różnicowania komórek nabłonkowych. Proteiny p63 coraz częściej są wykorzystywane w diagnostyce nowotworów skóry, układu rozrodczego, sutka, głowy i szyi oraz płuc.ABSTRACT p63 proteins are p53 homologs, and with p73 belong to the p53 family. These transcription factors regulate metabolism, proliferation, differentiation, aging and cell death. p63 is crucial for development and maintenance of squamous epithelium, and plays an important role in cancerogenesis. p63 exists in multiple isoforms belonging to 2 main groups: TAp63 and ΔNp63. TAp63 are expressed at very low levels (except for oocytes). ΔNp63 isoforms are predominant isoforms overexpressed in basal epithelial cells of skin, appendages, breast, prostate, and urinary tract. In contrast to TAp63, they are believed to act as oncoproteins. In the female genital tract p63 may be a very useful marker for distinguishing problematic cancers, when diagnosis determines the therapeutic management. It seems that p63 is necessary for activation of HPV late gene expression upon epithelial proliferation and differentiation. p63 is increasingly being taken into account in the diagnosis of epithelial tumors of skin, genital tract, breast, head, neck and lungs.Rola białek p63 w kancerogenezie oraz znaczenie ich ekspresji w diagnostyce nowotworów skóry i żeńskiego układu rozrodczegoThe role of p63 proteins in tumorigenesis and the significance of their expression in the diagnosis of skin and female genital tract neoplasms

show abstract

Identification of a Basal/Reserve Cell Immunophenotype in Benign and Neoplastic Endometrium: A Study with the p53 Homologue p63

Cited by 65 publications

References 11 publications

p63 Immunohistochemistry in the distinction of adenoid cystic carcinoma from basaloid squamous cell carcinoma

p63 Immunohistochemistry in the distinction of adenoid cystic carcinoma from basaloid squamous cell carcinoma

Expression and Regulation of the ΔN and TAp63 Isoforms in Salivary Gland Tumorigenesis

The role of p63 proteins in tumorigenesis and the significance of their expression in the diagnosis of skin and female genital tract neoplasms

Contact Info

Product

Resources

About