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dc.creatorKanavaros, P.en
dc.creatorStefanaki, K.en
dc.creatorVlachonikolis, J.en
dc.creatorPapalazarou, D.en
dc.creatorRontogianni, D.en
dc.creatorArvanitis, D.en
dc.creatorAntonakopoulos, G.en
dc.creatorGorgoulis, V.en
dc.creatorBai, M.en
dc.creatorAgnantis, N. J.en
dc.date.accessioned2015-11-23T10:32:23Z
dc.date.available2015-11-23T10:32:23Z
dc.date.issued2000
dc.identifier.issn2507005
dc.identifier.urihttp://hdl.handle.net/11615/28867
dc.description.abstractThe aim of this study was to investigate the immunohistochemical expression of the proteins p53, Waf-l/p21, Rb, p16 and Ki67 in 38 cases of multiple myelomas (MM) and 4 cases of solitary extramedullary plasmacytomas in relation to the tumor histological grade and stage. In bone marrow (BM) biopsies from MM, overexpression of p53 and p21 proteins, in comparison to plasma cell infiltrates in non-pathological bone marrow, was detected in 13 out of 38 and 21 out of 38 cases, respectively. The combined immunoexpression of p53 and p21 proteins in the 38 cases of MM showed the following patterns: a) p53+/p21+ (13 cases) b) p53-/p21+ (8 cases) and c) p53-/p21- (17 cases). Rb, p16 and Ki67 proteins were detected in tumor cells in all 38 cases and their expression increased proportionally to tumor grade. The 4 cases of solitary extramedullary plasmacytomas showed the p53+/p21+ pattern in 2 cases and the p53-/p21+ pattern in 2 cases, all of them displaying Rb, p16 and Ki67 expression in tumor cells. The pattern p53+/p21+ might represent cases with wild-type p53 able to induce p21 expression. However, in previous studies p53 mutations were reported in about 3-10% of MM, and they were strongly associated with advanced disease. Thus, in some p53+/p21+ cases associated with high p53 expression and advanced disease, p53 gene cannot be excluded and up-regulation of p21 expression may be p53- independent. P53 overexpression correlated with increased tumor grade (p<0.005), advanced histological stage (p<0.001) and Ki67 expression in more than 10% of tumor cells (p<0.001). Since increase in Ki67 expression also correlated with increased tumor grade (p<0.001) and advanced histological stage (p<0.001), these findings suggest that impairment of the p53 growth control pathway is associated with tumor progression in MM. Thus, p53 and Ki67 immunostaining in routine BM biopsies may be helpful for the detection of MM with potentially aggressive behavior. Overexpression of p21 in MM correlated with higher Ki67 expression (p<0.005), suggesting that the p21 function of arresting cell-cycle is impaired. Ki-67 expression in MM increased in parallel with p16 (p<0.001) and Rb expression (p<0.001). Rb expression could represent a growth control response which, however, might not be able to induce growth arrest in view of the parallel increase in Ki67 expression and of previous findings showing that Rb protein in MM cells is expressed mostly in its phosphorylated form.en
dc.source.urihttp://www.scopus.com/inward/record.url?eid=2-s2.0-0034351760&partnerID=40&md5=3b2a4334ee60ce9a01956938015fccde
dc.subjectCell cycle proteinsen
dc.subjectImmunohistochemistryen
dc.subjectMyelomasen
dc.subjectKi 67 antigenen
dc.subjectprotein p16en
dc.subjectprotein p21en
dc.subjectprotein p53en
dc.subjectCDKN1A protein, humanen
dc.subjectcyclin dependent kinase inhibitor 1Aen
dc.subjectcyclineen
dc.subjectprotein p16INK4aen
dc.subjectretinoblastoma proteinen
dc.subjecttumor proteinen
dc.subjectadvanced canceren
dc.subjectarticleen
dc.subjectbone marrow biopsyen
dc.subjectcancer gradingen
dc.subjectcancer inhibitionen
dc.subjectcancer stagingen
dc.subjectcell infiltrationen
dc.subjectcontrolled studyen
dc.subjectgene expressionen
dc.subjecthumanen
dc.subjecthuman tissueen
dc.subjectmultiple myelomaen
dc.subjectplasmacytomaen
dc.subjectpriority journalen
dc.subjectprotein phosphorylationen
dc.subjecttumor cellen
dc.subjecttumor growthen
dc.subjecttumor suppressor geneen
dc.subjectchemistryen
dc.subjectCyclin-Dependent Kinase Inhibitor p16en
dc.subjectCyclin-Dependent Kinase Inhibitor p21en
dc.subjectCyclinsen
dc.subjectHumansen
dc.subjectKi-67 Antigenen
dc.subjectNeoplasm Proteinsen
dc.subjectTumor Suppressor Protein p53en
dc.titleImmunohistochemicall expression of the p53, p21/Waf-1, Rb, p16 and Ki67 proteins in multiple myelomaen
dc.typejournalArticleen


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