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Scheda a cura di Marco Chilosi e Claudio Doglioni (GYM) p63 PATOLOGIA TIMICA
L'epitelio timico normale, in tutte le sue componenti (sucapsulare, corticale e midollare) esprime DN-p63 nucleare
Analogamente alla citocheratina-5 (identificabile con anticorpi 34bE12 o specifici per CK5) p63 è un ottimo marcatore delle cellule epiteliali del timo. L'espressione è conservata nella trasformazione neoplastica.
TUTTI i timomi ed i carcinomi timici dimostrano intensa espressione di p63 nel 100% delle cellule neoplastiche, indipendentemente dall'stotipo
figura 1. Timoma B3 (WDTC): intensa espressione nucleare di p63 (DN-p63) nelle cellule neoplastiche
Virchows Arch. 2003 Jul 8 [Epub ahead of print]. Constitutive expression of DeltaN-p63alpha isoform in human thymus and thymic epithelial tumours. Chilosi M, Zamo A, Brighenti A, Malpeli G, Montagna L, Piccoli P, Pedron S, Lestani M, Inghirami G, Scarpa A, Doglioni C, Menestrina F. Department of Pathology, University of Verona, Policlinico G.B.Rossi, Strada Le Grazie 8, 37134, Verona, Italy. p63, a member of the p53 family, is involved in the survival and differentiation of reserve/stem cells in different epithelia. To unveil the possible role of p63 in thymic physiology and pathology, we investigated the expression of p63 isoforms in normal thymus, thymomas and other mediastinal tumours. All samples were analysed using immunohistochemistry with three different antibodies: 4A4 antibody recognising all p63 isoforms, p40 antibody reacting only with truncated dominant-negative isoforms (DeltaN-p63) and H-129 antibody recognising all alpha-isoforms. Reverse-transcription polymerase chain reaction (RT-PCR), and real-time PCR analyses were performed on RNA extracted from frozen samples of four thymomas and two primary-mediastinal large-B-cell lymphoma (PMLBCL). In normal thymus, DeltaN-p63alpha was expressed in all cortical and medullary epithelial cells, with decreasing intensity in Hassall's corpuscles. This phenotype was conserved in neoplastic transformation since all 54 investigated thymomas (World Health Organization types A, AB, B1, B2, B3, C) expressed DeltaN-p63alpha (virtually 100% cells). The predominance of DeltaN-p63alpha isoform mRNA was confirmed by real-time PCR. Among other mediastinal tumours, DeltaN-p63alpha was only expressed in those displaying either a stratified epithelial component (teratomas) or epidermoid differentiation (lung carcinoma). Among lymphomas, T-cell-precursor lymphomas did not express p63, whereas most PMLBCL expressed TA-p63alpha (7/8). PMID: 12851817 [PubMed - as supplied by publisher]
Clin Cancer Res. 2002 Feb;8(2):494-501. p63 expression profiles in human normal and tumor tissues. Di Como CJ, Urist MJ, Babayan I, Drobnjak M, Hedvat CV, Teruya-Feldstein J, Pohar K, Hoos A, Cordon-Cardo C. Division of Molecular Pathology, Department of Pathology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. PURPOSE: The p63 gene, located on chromosome 3q27-28, is a member of the p53 gene family. The product encoded by the p63 gene has been reported to be essential for normal development. EXPERIMENTAL DESIGN: In this study, we examined the expression pattern of p63 in human normal and tumor tissues by immunohistochemistry using a monoclonal antibody (clone 4A4) that recognizes all p63 splice variants, and by reverse transcription-PCR using isoform-specific primers. RESULTS: We found that 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. Consistent with the phenotype observed in normal tissues, we found that p63 is expressed predominantly in basal cell and squamous cell carcinomas, as well as transitional cell carcinomas, but not in adenocarcinomas, including those of breast and prostate. Interestingly, thymomas expressed high levels of p63. Moreover, a subset of non-Hodgkin's lymphoma was also found to express p63. Using isoform-specific reverse transcription-PCR, we found that thymomas express all isoforms of p63, whereas the non-Hodgkin's lymphoma tended to express the transactivation-competent isoforms. We did not detect p63 expression in a variety of endocrine tumors, germ cell neoplasms, or melanomas. Additionally, soft tissue sarcomas were also found to have undetectable p63 levels. CONCLUSIONS: Our data support a role for p63 in squamous and transitional cell carcinomas, as well as certain lymphomas and thymomas. PMID: 11839669 [PubMed - indexed for MEDLINE]
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