title: Gene expression profiling indicates that immunohistochemical expression of CD40 is a marker of an inflammatory reaction in the tumor stroma of diffuse large B-cell lymphoma.
abstract: Immunohistochemical expression of CD40 is seen in 60-70% of diffuse large B-cell lymphoma (DLBCL) and is associated with a superior prognosis. By using gene expression profiling we aimed to further explore the underlying mechanisms for this effect. Ninety-eight immunohistochemically defined CD40 positive or negative DLBCL tumors, 63 and 35 respectively, were examined using spotted 55K oligonucleotide arrays. CD40 expressing tumors were characterized by up-regulated expression of genes encoding proteins involved in cell-matrix interactions: collagens, integrin αV, proteoglycans and proteolytic enzymes, and antigen presentation. Immunohistochemistry confirmed that CD40 positive tumors co-express the proinflammatory proteoglycan biglycan (p = 0.005), which in turn correlates with the amount of infiltrating macrophages and CD4 and CD8 positive T-cells. We postulate that immunohistochemical expression of CD40 mainly reflects the inflammatory status in tumors. A high intratumoral inflammatory reaction may correlate with an increased autologous tumor response, and thereby a better prognosis.
authors.affiliation: Department of Oncology, Institution of Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden. karin.rydstrom@med.lu.se
authors.forename: Karin
authors.initials: K
authors.lastname: Rydström
authors.forename: Patrick
authors.initials: P
authors.lastname: Joost
authors.forename: Mats
authors.initials: M
authors.lastname: Ehinger
authors.forename: Patrik
authors.initials: P
authors.lastname: Edén
authors.forename: Mats
authors.initials: M
authors.lastname: Jerkeman
authors.forename: Eva
authors.initials: E
authors.lastname: Cavallin-Ståhl
authors.forename: Johan
authors.initials: J
authors.lastname: Linderoth
mesh_terms: D058578:Biglycan / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D019013:CD40 Antigens / Q000235:genetics* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D039564:Integrin alphaV / Q000235:genetics / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D058578:Biglycan; D014408:Biomarkers, Tumor; D019013:CD40 Antigens; D039564:Integrin alphaV; D055293:Receptors, Urokinase Plasminogen Activator