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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4784-4791.
Prepublished online as a Blood First Edition Paper on February 24, 2005; DOI 10.1182/blood-2004-11-4201.
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Submitted November 3, 2004
Accepted February 10, 2005
Cyclooxygenase-2 (COX-2) is frequently expressed in multiple myeloma and is an independent predictor of poor outcome
Marco Ladetto*, Sonia Vallet, Andreas Trojan, Maria Dell'Aquila, Luigia Monitillo, Rosalba Rosato, Loredana Santo, Daniela Drandi, Alessandra Bertola, Patrizia Falco, Federica Cavallo, Irene Ricca, Federica De Marco, Barbara Mantoan, Beata Bode-Lesniewska, Gloria Pagliano, Roberto Francese, Alberto Rocci, Monica Astolfi, Mara Compagno, Sara Mariani, Laura Godio, Lydia Marino, Marina Ruggeri, Paola Omede, Antonio Palumbo, and Mario Boccadoro
Divisione di Ematologia, Dipartimento di Medicina ed Oncologia Sperimentale, Universita di Torino, Azienda Ospedaliera San Giovanni Battista, Torino, Italy
Department of Oncology, University Hospital, Zurich, Switzerland
Servizio di Epidemiologia dei Tumori e Biostatistica, Universita di Torino, Azienda Ospedaliera San Giovanni Battista, Torino, Italy
Department of Pathology, University Hospital, Zurich, Switzerland
Divisione di Ematologia, Dipartimento di Medicina ed Oncologia Sperimentale, Universita di Torino, Azienda Ospedaliera San Giovanni Battista, Torino, Italy; Centro di Ricerca in Medicina Sperimentale (CERMS), Ospedale San Giovanni Battista, Torino, Italy
Divisione di Anatomia Patologica, Dipartimento di Scienze Biomediche ed Oncologia Umana, Universita di Torino, Azienda Ospedaliera San Giovanni Battista, Torino, Italy
* Corresponding author; email: marco.ladetto{at}unito.it.
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 hematological 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. 142 bone marrow (BM) specimens, including MM and MGUS, were evaluated by Western blotting (WB). Selected cases underwent further evaluation by WB on purified CD138 positive cells, immunohistochemistry (IC) and real time 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<0.001) and overall survival (28 vs. 52 months, p<0.05). Real-time PCR showed COX-2 mRNA over-expression. 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 hematological tumors and its potential use as a therapeutic or chemo-preventive target in onco-hematology.

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