Blood, 15 November 2006, Vol. 108, No. 10, pp. 3514-3519.
Prepublished online as a Blood First Edition Paper on July 25, 2006; DOI 10.1182/blood-2006-04-015305.
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NEOPLASIA
Prognostic significance of metallothionein in B-cell lymphomas
Christian Bjørn Poulsen,
Rehannah Borup,
Niels Borregaard,
Finn Cilius Nielsen,
Michael Boe Møller, and
Elisabeth Ralfkiaer
From the Department of Pathology, the Department of Clinical Biochemistry, and the Department of Hematology, Copenhagen University Hospital, Rigshospitalet, Denmark; and the Department of Pathology, Odense University Hospital, Odense, Denmark.
We have investigated metallothionein (MT) I and II mRNA and protein in B-cell lymphomas with particular reference to diffuse large B-cell lymphoma (DLBCL). The mRNA profiling was performed on Affymetrix arrays and showed up-regulated MT mRNA in 15 of 48 DLBCLs, including 12 of 23 activated B-cell (ABC) and 3 of 9 type-3 lesions. In contrast, MT mRNA was low to undetectable in 16 germinal center B-cell (GCB)-type DLBCLs. Only 1 of 15 patients with up-regulated MT mRNA achieved a sustained remission, suggesting that up-regulated MT mRNA constitutes a significant risk factor for treatment failure. This was confirmed in 2 independent series, which showed significantly shorter 5-year survival in DLBCL with high versus low MT-IIa levels. By immunohistology, MT was shown to be present in both macrophages and lymphoma cells. The proportion of MT-positive macrophages did not correlate with the survival. In contrast, in 115 DLBCLs, MT labeling of more than 20% lymphoma cells was associated with a significantly poorer 5-year survival, independent of the age, stage, or International Prognostic Index. Taken together, it is suggested that both increased MT mRNA and MT protein expression by more than 20% lymphoma cells constitute independent risk factors in DLBCL.
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