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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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NEOPLASIA
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 Omedè,
Antonio Palumbo, and
Mario Boccadoro
From the Divisione di Ematologia, Dipartimento di Medicina ed Oncologia Sperimentale, and Servizio di Epidemiologia dei Tumori e Biostatistica, and Divisione di Anatomia Patologica, Dipartimento di Scienze Biomediche ed Oncologia Umana, and Centro di Ricerca in Medicina Sperimentale (CERMS), Università di Torino, Azienda Ospedaliera San Giovanni Battista, Torino, Italy; the Department of Oncology and Pathology, University Hospital Zürich, Switzerland.
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)
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