title: Lymphoma cell VEGFR2 expression detected by immunohistochemistry predicts poor overall survival in diffuse large B cell lymphoma treated with immunochemotherapy (R-CHOP).
abstract: Diffuse large B cell lymphoma (DLBCL) is clinically and biologically heterogeneous. In most cases of DLBCL, lymphoma cells co-express vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2, suggesting autocrine in addition to angiogenic effects. We enumerated microvessel density and scored lymphoma cell expression of VEGF, VEGFR1, VEGFR2 and phosphorylated VEGFR2 in 162 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone)-like regimens. VEGFR2 expression correlated with shorter overall survival (OS) independent of International Prognostic Index (IPI) (P = 0.0028). Phosphorylated VEGFR2 (detected in 13% of cases) correlated with shorter progression-free survival (PFS, P = 0.044) and trended toward shorter OS on univariate analysis. VEGFR1 was not predictive of survival on univariate analysis, but it did correlate with better OS on multivariate analysis with VEGF, VEGFR2 and IPI (P = 0.036); in patients with weak VEGFR2, lack of VEGFR1 coexpression was significantly correlated with poor OS independent of IPI (P = 0.01). These results are concordant with our prior finding of an association of VEGFR1 with longer OS in DLBCL treated with chemotherapy alone. We postulate that VEGFR1 may oppose autocrine VEGFR2 signalling in DLBCL by competing for VEGF binding. In contrast to our prior results with chemotherapy alone, microvessel density was not prognostic of PFS or OS with R-CHOP-like therapy.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, CA 94305-5324, USA.
authors.forename: Dita
authors.initials: D
authors.lastname: Gratzinger
authors.forename: Ranjana
authors.initials: R
authors.lastname: Advani
authors.forename: Shuchun
authors.initials: S
authors.lastname: Zhao
authors.forename: Neha
authors.initials: N
authors.lastname: Talreja
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Tibshirani
authors.forename: Ragini
authors.initials: R
authors.lastname: Shyam
authors.forename: Sandra
authors.initials: S
authors.lastname: Horning
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Sehn
authors.forename: Pedro
authors.initials: P
authors.lastname: Farinha
authors.forename: Javier
authors.initials: J
authors.lastname: Briones
authors.forename: Izidore S
authors.initials: IS
authors.lastname: Lossos
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Yasodha
authors.initials: Y
authors.lastname: Natkunam
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D011237:Predictive Value of Tests; D011241:Prednisone / Q000008:administration & dosage; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D000069283:Rituximab; D016019:Survival Analysis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D040262:Receptors, Vascular Endothelial Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2; D011241:Prednisone