title: Tenascin and microvessel stromal changes in patients with non-Hodgkin's lymphoma are isolated to the sites of disease and vary in correlation to disease activity.
abstract: This study investigated stromal changes in expression of tenascin and vasculogenesis in lymphoma. Documenting the dynamic nature of the stromal changes in lymphoma in relation to response to therapy is helpful in planning new therapies directed at these targets. Two hundred and sixty one samples from 111 patients with varying types of non-Hodgkin's lymphoma were reviewed and examined using immunohistochemistry techniques. Samples were stained for factor VIII - related antigen for microvessel density (MVD) analysis and anti-tenascin antibody for qualitative assessment of the stromal expression. Multiple samples from the same patient were taken at the same point in time to assess whether stromal changes were limited to sites of disease. Multiple samples were examined over the course of a patient's illness to assess whether the stromal changes were modulated according to disease activity. There was a significant increase in tenascin expression and MVD in the sites of disease compared with uninvolved sites (p = 0.01 and p < 0.0001, respectively). In patients who responded to therapy, there was a decrease in the expression of tenascin (p = 0.0049) and MVD (p < 0.0001), and in those with disease progression there was an increase in the tenascin expression (p = 0.0050) and MVD (p < 0.0001). Our results suggest stromal changes are isolated to the sites of disease within patients, allowing targeted therapies to be developed. Further, stromal changes correlate with disease response over the course of the patient's disease. This new finding may have implications for the timing of anti-stromally directed therapies.
authors.affiliation: Department of Medicine, Division of Oncology and Stem Cell Transplantation, Duke University Medical Center, Durham, NC 27710, USA. rizzi003@mc.duke.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Rizzieri
authors.forename: Martha
authors.initials: M
authors.lastname: Wadleigh
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Wikstrand
authors.forename: Karen P
authors.initials: KP
authors.lastname: Mann
authors.forename: Filiz
authors.initials: F
authors.lastname: Sen
authors.forename: Bercedis L
authors.initials: BL
authors.lastname: Peterson
authors.forename: Donna
authors.initials: D
authors.lastname: Niedzwiecki
authors.forename: Alan D
authors.initials: AD
authors.lastname: Proia
authors.forename: Darell D
authors.initials: DD
authors.lastname: Bigner
mesh_terms: D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology*; D001853:Bone Marrow / Q000098:blood supply; D018450:Disease Progression; D006801:Humans; D008198:Lymph Nodes / Q000098:blood supply; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism* / Q000473:pathology*; D008833:Microcirculation; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D019063:Tenascin / Q000378:metabolism*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019063:Tenascin