Metallothionein-I + II and receptor megalin are altered in relation to oxidative stress in cerebral lymphomas

Abstract

Primary central nervous system lymphoma (PCNSL) in immunocompetent patients is highly malignant and has a poor prognosis. The PCNSL molecular features are reminiscent to some degree of diffuse large B-cell lymphoma (DLBCL), yet PCNSL shows unique molecular profiles and a distinct clinical behavior. This article characterizes the histopathology and expression profiles of metallothionein-I + II (MT-I + II) and their receptor megalin along with proliferation, oxidative stress, and apoptosis in PCNSL and in central nervous system (CNS) lymphomas due to relapse from DLBCL (collectively referred to as CNS lymphoma). We show for the first time that MT-I + II and megalin are significantly altered in CNS lymphoma relative to controls (reactive lymph nodes and non-lymphoma brain tissue with neuropathology). MT-I + II are secreted in the CNS and are found mainly in the lymphomatous cells, while their receptor megalin is increased in cerebral cells. This morphology likely reflects the CNS lymphoma microenvironment and molecular interactions between lymphomatous and neuronal cells.

Keywords:

• Neoplasm
• Hematology
• Neuropathology
• Oxidative stress

Declaration of Interest: We gratefully acknowledge the financial support from: Hørslev Fonden, Fonden af 17-12-1981, Forskningsrådet på Amtssygehuset i Herlev, Det Frie forskningsråd, IMK Almene Fond, Aase and Ejnar Danielsens Fond, Dir. Madsens Fond, Fonden til Lægevidenskabens Fremme, Kathrine og Vigo Skovgaards Fond, Fru Lily Benthine Lunds Fond, Toyota Fonden, Hotelejer Edvard Johnsen og hustrus fond, Tolstrups Fond, Lægeforeningens Forskningsfond, Dir. Ib Henriksens Fond, Lægernes Forsikringsforening, the Medical Society in Copenhagen, and the Agnethe Løvgreens Foundation.