Submitted April 11, 2006
Accepted June 29, 2006
Prognostic significance of metallothionein in
B-cell lymphomas
Christian Bjorn Poulsen*, Rehannah Borup, Niels Borregaard, Finn Cilius Nielsen, Michael Boe Moller, and Elisabeth Ralfkiaer
Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Denmark
Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Denmark
Department of Hematology, Copenhagen University Hospital, Rigshospitalet, Denmark
Department of Pathology, Odense University Hospital, Denmark
* Corresponding author; email: c.poulsen{at}rh.dk.
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 ar-rays and showed upregulated MT mRNA in 15 of 48 DLBCL, including 12 of 23 ABC and 3 of 9 type-3 le-sions. By contrast MT mRNA was low to undetectable in 16 GCB-type DLBCL. Only one of 15 patients with upregulated MT mRNA achieved a sustained remission, suggesting that upregulated MT mRNA constitutes a significant risk factor for treatment failure. This was confirmed in two independent series (Rosenwald et al. 2005; Monti et al. 2005), which showed significantly shorter 5-year survival in DLBCL with high vs. low MTIIa 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. By contrast, in 115 DLBCL MT-labeling of > 20% lymphoma cells was associated with a significantly poorer 5-year survival, independ-ent of the age, stage or International Prognostic Index. Taken together, it is suggested that both increased MT mRNA and MT protein expression by > 20% lymphoma cells constitute independent risk factors in DLBCL.
