p63 Is a Prostate Basal Cell Marker and Is Required for Prostate Development

Signoretti, Sabina; Waltregny, David; Dilks, James R.; Isaac, Beth; Lin, Douglas I.; Garraway, Levi A.; Yang, Annie; Montironi, R; McKeon, Frank; Loda, Massimo

doi:10.1016/s0002-9440(10)64814-6

Cited by 540 publications

(477 citation statements)

References 25 publications

(34 reference statements)

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“…Owing to the predominant mRNA expression of DN isoforms rather than TA isoforms in normal urothelial cells and low-grade urothelial tumour cells, our results suggest that DNp63a is the predominant isoform in these cell lines. These results are consistent with published data in human keratinocytes (Yang et al, 1998) and human prostate basal cells (Signoretti et al, 2000).…”

Section: Expression Of P63 In Cultured Human Normal and Neoplastic Ursupporting

confidence: 94%

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Impaired ΔNp63 expression associates with reduced β-catenin and aggressive phenotypes of urothelial neoplasms

et al. 2003

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p63, a homologue of the p53 gene, is considered to be essential for the normal development of stratified epithelia including urothelium. To examine possible roles of p63 in urothelial tumorigenesis, p63 expression was systematically examined in normal urothelium, low-grade papillary noninvasive (LPN) urothelial tumours, and high-grade or invasive carcinomas, using either an isoformnonspecific or a DN-isoform-specific antibody. Expression profiles of p63 were also analysed in cultured cells. Immunoreactivity with the two antibodies was virtually identical in tissue samples examined. Basal and intermediate cell layers of normal urothelium showed intense nuclear p63 immunostaining. This normal staining pattern was preserved in a majority of LPN tumours, whereas it was frequently impaired in high-grade or muscle-invasive carcinomas. At the mRNA level, DNp63 expression predominated over TAp63, and amounts of DNp63 mRNA correlated with p63 immunoreactivity, confirming that DNp63 accounts for p63 expressed in urothelial tissues. In cultured cells, DNp63 was also expressed in low-grade tumour cells as well as normal urothelial cells, but undetectable in high-grade aggressive carcinoma cells. Interestingly, impaired DNp63 expression significantly associated with reduced b-catenin expression that was possibly related to progression of urothelial neoplasms. Thus, impaired DNp63 expression characterises aggressive phenotypes of urothelial neoplasms.

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Section: Expression Of P63 In Cultured Human Normal and Neoplastic Ursupporting

confidence: 94%

“…In negative controls, the primary antibody was substituted for nonimmune mouse sera. Nonneoplastic prostate glands were used as positive controls (Signoretti et al, 2000). The slides were independently reviewed by two of the authors (KF and KS) who were blinded to the clinicopathologic data.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Impaired ΔNp63 expression associates with reduced β-catenin and aggressive phenotypes of urothelial neoplasms

et al. 2003

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“…The truncated forms are thought to inhibit cell cycle arrest and apoptosis driven by transactivating p63/p53 interaction. 12 The truncated isoforms are preferentially expressed in the basal cell compartment of normal epithelium 12,13 and transactivating forms are more widely distributed in benign and neoplastic epithelium. 14 Consequently, different isoforms of p63 appear to play a role in maintaining the epithelial stem cell population, spurring epithelial differentiation and inducing neoplasia.…”

Section: Discussionmentioning

confidence: 99%

p63 expression in assessment of bronchioloalveolar proliferations of the lung

et al. 2004

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Discrimination of well-differentiated pulmonary adenocarcinoma from reactive bronchioloalveolar epithelium can be difficult on routine histology, especially with small biopsies. Ancillary studies to help in this distinction are desirable. p63, a p53-homologous nuclear protein, is a marker of reserve cells of the bronchus and terminal lobular unit. In this study, 33 cases of adenocarcinoma (20 open lung and 13 transbronchial/percutaneous biopsies) and 43 cases of benign lungs with fibrosis and metaplasia (22 open lung and 21 transbronchial/ percutaneous biopsies) were studied for nuclear p63 expression by immunohistochemistry (Dako, Carpinteria, CA, USA). Five additional cases each of atypical adenomatous hyperplasia and adenosquamous carcinoma and three cases of squamous carcinoma (all open lung biopsies) were also stained. The diagnostic categories of benign lung conditions were usual interstitial pneumonia, parenchymal scar, cryptogenic organizing pneumonia and diffuse alveolar damage. In neoplastic cases, p63 positivity was calculated as percentage of all tumor cells examined. In areas of normal lung, p63 decorated the reserve cells of large and small airways and occasional cells of the distal lobular unit. In fibrotic reactive processes, an interrupted but distinct pattern of nuclear staining was present in all cases, with staining of basal cells of the airways as well as bronchiolar-and squamous-metaplastic epithelium (43/43, 100%). p63 immunoreactivity was less uniform in areas of acute lung injury within these cases. One adenocarcinoma and two cases of atypical adenomatous hyperplasia showed strong immunoreactivity (480%), while three adenocarcinomas highlighted only rare tumor nuclei (o5% of tumor cells). Morphologic areas where p63 immunostaining was not helpful included the junction of normal lung and lepidic growth of adenocarcinoma, and retrograde spread of adenocarcinoma into small airways. Our results highlight the differential expression of p63 across various bronchioloalveolar lesions. Moreover, p63 may be helpful in distinguishing reactive from neoplastic glandular proliferations in the lung.

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“…7,8 Previous studies in several laboratories have shown p63 expression in many normal tissues including squamous epithelia, urothelium, bronchial epithelium, and the myoepithelial layers of breast, prostate and submucosal glands. [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.…”

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confidence: 99%

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

et al. 2005

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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.

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p63 Is a Prostate Basal Cell Marker and Is Required for Prostate Development

Cited by 540 publications

References 25 publications

Impaired ΔNp63 expression associates with reduced β-catenin and aggressive phenotypes of urothelial neoplasms

Impaired ΔNp63 expression associates with reduced β-catenin and aggressive phenotypes of urothelial neoplasms

p63 expression in assessment of bronchioloalveolar proliferations of the lung

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

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