Cyclooxygenase-2 (COX-2) is frequently expressed in multiple myeloma and is an independent predictor of poor outcome

Cyclooxygenase 2 (COX-2) is an inflammation-associated enzyme involved in the pathogenesis of many solid tumors, but little is known about its presence and role in hematologic neoplasms. Multiple myeloma (MM) is known to involve a deregulated cytokine network with secretion of inflammatory mediators...

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Bibliographic Details
Published in:Blood 2005-06, Vol.105 (12), p.4784-4791
Main Authors: Ladetto, Marco, Vallet, Sonia, Trojan, Andreas, Dell'Aquila, Maria, Monitillo, Luigia, Rosato, Rosalba, Santo, Loredana, Drandi, Daniela, Bertola, Alessandra, Falco, Patrizia, Cavallo, Federica, Ricca, Irene, De Marco, Federica, Mantoan, Barbara, Bode-Lesniewska, Beata, Pagliano, Gloria, Francese, Roberto, Rocci, Alberto, Astolfi, Monica, Compagno, Mara, Mariani, Sara, Godio, Laura, Marino, Lydia, Ruggeri, Marina, Omedè, Paola, Palumbo, Antonio, Boccadoro, Mario
Format: Article
Language:English
Subjects:
Adult
Aged
Biological and medical sciences
Blotting, Western
Bone Marrow Cells - cytology
Bone Marrow Cells - metabolism
Cell Line, Tumor
Cyclooxygenase 2
Disease-Free Survival
DNA, Complementary - metabolism
Drug Resistance, Neoplasm
Female
Hematologic and hematopoietic diseases
Humans
Immunodeficiencies. Immunoglobulinopathies
Immunoglobulinopathies
Immunohistochemistry
Immunopathology
Inflammation
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Male
Medical sciences
Membrane Glycoproteins - biosynthesis
Membrane Proteins
Middle Aged
Multiple Myeloma - diagnosis
Multiple Myeloma - enzymology
Prognosis
Prostaglandin-Endoperoxide Synthases - biosynthesis
Proteoglycans - biosynthesis
Recurrence
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
Syndecan-1
Syndecans
Time Factors
Treatment Outcome
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Summary:Cyclooxygenase 2 (COX-2) is an inflammation-associated enzyme involved in the pathogenesis of many solid tumors, but little is known about its presence and role in hematologic neoplasms. Multiple myeloma (MM) is known to involve a deregulated cytokine network with secretion of inflammatory mediators. We thus decided to investigate the involvement of COX-2 in this neoplasm. Western blotting (WB) was used to evaluate 142 bone marrow (BM) specimens, including MM and monoclonal gammopathy of undetermined significance (MGUS). Selected cases under-went further evaluation by WB on purified CD138+ cells, immunohistochemistry (IC), and real-time polymerase chain reaction (PCR) for mRNA expression. COX-2 was expressed in 11% (2 of 18) of MGUS specimens, 31% (29 of 94) of MM at diagnosis, and 47% (14 of 30) of MM with relapsed/refractory disease. COX-2 positivity was associated with a poor outcome in terms of progression-free (18 vs 36 months; P < .001) and overall survival (28 vs 52 months; P < .05). Real-time PCR showed COX-2 mRNA overexpression. IC and cell separation studies demonstrated COX-2 expression to be restricted to malignant plasma cells. This is the first report of the presence and prognostic role of COX-2 expression in MM. Future studies will assess COX-2 involvement in other hematologic tumors and its potential use as a therapeutic or chemo-preventive target in onco-hematology. (Blood. 2005; 105:4784-4791)
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2004-11-4201