title: Prognostic significance of metallothionein in B-cell lymphomas.
abstract: 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.
authors.affiliation: Department of Pathology 5444, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Kbh Ø, Denmark. c.poulsen@rh.dk
authors.forename: Christian Bjørn
authors.initials: CB
authors.lastname: Poulsen
authors.forename: Rehannah
authors.initials: R
authors.lastname: Borup
authors.forename: Niels
authors.initials: N
authors.lastname: Borregaard
authors.forename: Finn Cilius
authors.initials: FC
authors.lastname: Nielsen
authors.forename: Michael Boe
authors.initials: MB
authors.lastname: Møller
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ralfkiaer
mesh_terms: D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000401:mortality; D008668:Metallothionein / Q000032:analysis* / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D016019:Survival Analysis; D017211:Treatment Failure; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D008668:Metallothionein