p53 nuclear accumulation is associated with extramedullary progression of multiple myeloma.
Progression of multiple myeloma (MM) from intramedullary to extramedullary sites heralds an aggressive phase of the disease but to the best of our knowledge, biologic factors have not been studied in paired biopsies from medullary and extramedullary sites. In this study, we immunostained paired bone marrow and extramedullary biopsies from 12 cases of MM for p53, CD56 and MIB-1 (proliferative index). In addition, 22 cases of extramedullary plasmacytoma (EMP) without bone marrow involvement were included as a control group. p53 nuclear accumulations were detected in myeloma cells derived from the extramedullary sites in 9 (75%) of the 12 cases, whereas only 1 of (8%) 12 bone marrow myeloma specimens expressed p53 (P = 0.003). p53 expression was also more prevalent in extramedullary sites of MM than EMP (75% vs. 18%, P = 0.003). There was no significant difference in CD56 expression between intramedullary and extramedullary MM (17% vs. 33%, P = 0.64), or between intramedullary MM and EMP (17% vs. 38%, P = 0.25). The MIB-1 proliferation index increased significantly as plasma cells migrated from the bone marrow microenvironment to extramedullary sites (P = 0.0001). Our data indicates that p53 nuclear expression but not CD56 expression, along with increased proliferation index is associated with disease progression from intramedullary to extramedullary sites in MM.
Sheth
Neil
N
Department of Laboratory Hematology, University Health Network, Toronto, ON, Canada.
Yeung
Joanna
J
Chang
Hong
H
D000328:Adult; D000368:Aged; D001706:Biopsy; D019002:CD56 Antigen / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D017384:Sequence Deletion; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
D019002:CD56 Antigen; D016159:Tumor Suppressor Protein p53; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases