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. 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.
Ladetto
Marco
M
Dipartimento di Medicina ed Oncologia Sperimentale, Servizio di Epidemiologia dei Tumori e Biostatistica, Centro di Ricerca in Medicina Sperimentale, Università di Torino, Azienda Ospedaliera San Giovanni Battista, Torino, Italy. marco.ladetto@unito.it
Vallet
Sonia
S
Trojan
Andreas
A
Dell'Aquila
Maria
M
Monitillo
Luigia
L
Rosato
Rosalba
R
Santo
Loredana
L
Drandi
Daniela
D
Bertola
Alessandra
A
Falco
Patrizia
P
Cavallo
Federica
F
Ricca
Irene
I
De Marco
Federica
F
Mantoan
Barbara
B
Bode-Lesniewska
Beata
B
Pagliano
Gloria
G
Francese
Roberto
R
Rocci
Alberto
A
Astolfi
Monica
M
Compagno
Mara
M
Mariani
Sara
S
Godio
Laura
L
Marino
Lydia
L
Ruggeri
Marina
M
Omedè
Paola
P
Palumbo
Antonio
A
Boccadoro
Mario
M
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2; D018076:DNA, Complementary / Q000378:metabolism; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008565:Membrane Proteins; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000201:enzymology*; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011509:Proteoglycans / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053668:Syndecan-1; D053667:Syndecans; D013997:Time Factors; D016896:Treatment Outcome
D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases