title: Similar chemokine receptor profiles in lymphomas with central nervous system involvement - possible biomarkers for patient selection for central nervous system prophylaxis, a retrospective study.
abstract: Central nervous system (CNS) relapse occurs in around 5% of diffuse large B-cell lymphoma (DLBCL) cases. No biomarkers to identify high-risk patients have been discovered. We evaluated the expression of lymphocyte-guiding chemokine receptors in systemic and CNS lymphomas. Immunohistochemical staining for CXCR4, CXCR5, CCR7, CXCL12, and CXCL13 was performed on 89 tissue samples, including cases of primary central nervous system lymphoma (PCNSL), secondary CNS lymphoma (sCNSL), and systemic DLBCL. Also, 10 reactive lymph node samples were included. Immunoelectron microscopy was performed on two PCNSLs, one sCNSL, one systemic DLBCL, and one reactive lymph node samples, and staining was performed for CXCR4, CXCR5, CXCL12, and CXCL13. Chi-square test was used to determine correlations between clinical parameters, diagnostic groups, and chemokine receptor expression. Strong nuclear CXCR4 positivity correlated with systemic DLBCL, whereas strong cytoplasmic CXCR5 positivity correlated with CNS involvement (P = 0.003 and P = 0.039). Immunoelectron microscopy revealed a nuclear CXCR4 staining in reactive lymph node, compared with cytoplasmic and membranous localization seen in CNS lymphomas. We found that CNS lymphoma presented a chemokine receptor profile different from systemic disease. Our findings give new information on the CNS tropism of DLBCL and, if confirmed, may contribute to more effective targeting of CNS prophylaxis among patients with DLBCL.
authors.affiliation: Department of Oncology and Radiotherapy, Institute of Clinical Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Siria A
authors.initials: SA
authors.lastname: Lemma
authors.affiliation: Department of Oncology and Radiotherapy, Institute of Clinical Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Anna Kaisa
authors.initials: AK
authors.lastname: Pasanen
authors.affiliation: Department of Oncology and Radiotherapy, Institute of Clinical Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland.|Department of Pathology, Institute of Diagnostics, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Kirsi-Maria
authors.initials: KM
authors.lastname: Haapasaari
authors.affiliation: Department of Oncology and Radiotherapy, Institute of Clinical Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Sippola
authors.affiliation: Department of Pathology, Institute of Diagnostics, University of Oulu and Oulu University Hospital, Oulu, Finland.|Biocenter Oulu, University of Oulu, Oulu, Finland.
authors.forename: Raija
authors.initials: R
authors.lastname: Sormunen
authors.affiliation: Department of Clinical Pathology and Forensic Medicine, University of Eastern Finland, Cancer Center of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
authors.affiliation: Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Esa
authors.initials: E
authors.lastname: Jantunen
authors.affiliation: Department of Otorhinolaryngology, Institute of Clinical Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Koivunen
authors.affiliation: Department of Neurosurgery, Institute of Clinical Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Niina
authors.initials: N
authors.lastname: Salokorpi
authors.affiliation: Medical Informatics and Statistics Research Group, University of Oulu, Oulu, Finland.
authors.forename: Risto
authors.initials: R
authors.lastname: Bloigu
authors.affiliation: Department of Oncology and Radiotherapy, Institute of Clinical Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Taina
authors.initials: T
authors.lastname: Turpeenniemi-Hujanen
authors.affiliation: Department of Oncology and Radiotherapy, Institute of Clinical Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Kuittinen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers; D016022:Case-Control Studies; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary*; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008223:Lymphoma / Q000378:metabolism* / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011292:Premedication; D019707:Receptors, Chemokine / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D019707:Receptors, Chemokine
keywords: CXCR4; CXCR5; central nervous system prophylaxis; central nervous system relapse; central nervous system tropism; diffuse large B-cell lymphoma; primary central nervous system lymphoma; secondary Central nervous system lymphoma