Constitutive expression of ?N-p63? isoform in human thymus and thymic epithelial tumours

Chilosi, Marco; Zamò, Alberto; Brighenti, Alfredo; Malpeli, Giorgio; Montagna, Licia; Piccoli, P; Pedron, Serena; Lestani, Maurizio; Inghirami, Giorgio; Scarpa, Aldo; Doglioni, Claudio; Menestrina, Fabio

doi:10.1007/s00428-003-0857-4

Cited by 46 publications

(40 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

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

“…Consecutive sections of primary mediastinal large B-cell lymphoma and controls were analyzed with three TP73L-specific antibodies: the first (clone 4A4, IgG2a-Santa Cruz Biotechnology, Santa Cruz, CA, USA) reacts with all known variants of human TP73L; the second (p40, Oncogene Research Products, Boston, MA, USA) recognizes all DN-TP73L isoforms; the third (H-129 Santa Cruz Biotechnology) recognizes only a isoforms; 33,34 this antibody was tested only in primary mediastinal large B-cell lymphomas and in five diffuse large B-cell lymphomas. Only nuclear staining was interpreted as positive.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Technical details of the staining procedures have been previously described. [33][34][35] Double staining was performed as previously described. 34 All samples were processed using a semiautomated staining system (GenoMx i6000, BioGenex, San Ramon, CA, USA).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Expression of TP73L is a helpful diagnostic marker of primary mediastinal large B-cell lymphomas

et al. 2005

Self Cite

View full text Add to dashboard Cite

Primary mediastinal large B-cell lymphoma is a well-defined lymphoma entity whose molecular pathogenesis is incompletely understood and also lacking well-established diagnostic markers. Recently, the presence of overlapping features between classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma was highlighted by gene expression profiling as well as morphological studies. We investigated the expression of TP73L (commonly known as p63) isoforms in primary mediastinal large B-cell lymphoma at both protein and mRNA level, and demonstrated the exclusive presence of transactivating (TA) isoforms in all cases. We also demonstrated that TP73L is expressed in a subset of germinal center B-cells, as well as in some diffuse large B-cell lymphomas, but it is never present in classical Hodgkin lymphoma. Nodular lymphocyte predominant Hodgkin's lymphoma also showed TP73L positivity by immunohistochemistry. Isoform analysis by real-time PCR showed that TA-TP73La is the most represented in primary mediastinal large B-cell lymphoma, but TA-TP73Lc is the most differentially expressed in comparison to both germinal center B-cells and diffuse large B-cell lymphomas. TP73L expression proved a useful diagnostic marker of primary mediastinal large B-cell lymphoma, and gave new insights in to the molecular pathways playing a role in this lymphoma.

show abstract

“…9,12,14,16 Another important limitation of p63 as a 'squamous marker' is its unexpected expression in several other tumor types, particularly lymphomas, where reactivity has been reported in up to half of the cases. [19][20][21][22][23][24] This is a particularly treacherous pitfall with drastic treatment implications, as large cell lymphoma may present as a solitary thoracic mass, and its epithelioid morphology may closely mimic nonsmall cell carcinoma. [25][26][27] In this setting, strong expression of p63 could misclassify an unsuspected lymphoma as squamous cell carcinoma.…”

mentioning

confidence: 99%

p40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma

et al. 2012

View full text Add to dashboard Cite

Immunohistochemistry has recently emerged as a powerful ancillary tool for differentiating lung adenocarcinoma and squamous cell carcinoma-a distinction with important therapeutic implications. Although the most frequently recommended squamous marker p63 is extremely sensitive, it suffers from low specificity due to its reactivity in a substantial proportion of lung adenocarcinomas and other tumor types, particularly lymphomas. p40 is a relatively unknown antibody that recognizes DNp63-a p63 isoform suggested to be highly specific for squamous/basal cells. Here we compared the standard p63 antibody (4A4) and p40 in a series of 470 tumors from the archives of Memorial Sloan-Kettering Cancer Center and The Johns Hopkins Hospital, which included lung squamous cell carcinomas (n ¼ 81), adenocarcinomas (n ¼ 237), and large cell lymphomas (n ¼ 152). The p63 was positive in 100% of squamous cell carcinomas, 31% of adenocarcinomas, and 54% of large cell lymphomas (sensitivity 100%, specificity 60%). In contrast, although p40 was also positive in 100% of squamous cell carcinomas, only 3% of adenocarcinomas, and none of large cell lymphomas had p40 labeling (sensitivity 100%, specificity 98%). The mean percentage of p63 versus p40-immunoreactive cells in squamous cell carcinomas was equivalent (97 vs 96%, respectively, P ¼ 0.73). Rare adenocarcinomas with p40 labeling had reactivity in no more than 5% of tumor cells, whereas the mean (range) of p63-positive cells in adenocarcinomas and lymphomas was 26% (1-90%) and 48% (2-100%), respectively. In summary, p40 is equivalent to p63 in sensitivity for squamous cell carcinoma, but it is markedly superior to p63 in specificity, which eliminates a potential pitfall of misinterpreting a p63-positive adenocarcinoma or unsuspected lymphoma as squamous cell carcinoma. These findings strongly support the routine use of p40 in place of p63 for the diagnosis of pulmonary squamous cell carcinoma.

show abstract

Constitutive expression of ?N-p63? isoform in human thymus and thymic epithelial tumours

Cited by 46 publications

References 41 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 of TP73L is a helpful diagnostic marker of primary mediastinal large B-cell lymphomas

p40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma

Contact Info

Product

Resources

About