Lymphoma cell VEGFR2 expression detected by immunohistochemistry predicts poor overall survival in diffuse large B cell lymphoma treated with immunochemotherapy (R-CHOP)

Dita Gratzinger, Ranjana Advani, Shuchun Zhao, Neha Talreja, Robert J. Tibshirani, Ragini Shyam, Sandra Horning, Laurie H. Sehn, Pedro Farinha, Javier Briones, Izidore S. Lossos, Randy D. Gascoyne, Yasodha Natkunam

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)235-244
Number of pages10
JournalBritish Journal of Haematology
Volume148
Issue number2
DOIs
StatePublished - Jan 2010

Keywords

  • Angiogenesis
  • Non-Hodgkin lymphoma
  • Prognostic factors
  • Tumour biology
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'Lymphoma cell VEGFR2 expression detected by immunohistochemistry predicts poor overall survival in diffuse large B cell lymphoma treated with immunochemotherapy (R-CHOP)'. Together they form a unique fingerprint.

Cite this