Lymphoma cell VEGFR2 expression detected by immunohistochemistry predicts poor overall survival in diffuse large B cell lymphoma treated with immunochemotherapy (R-CHOP)
Por:
Gratzinger, D, Advani, R, Zhao, SC, Talreja, N, Tibshirani, RJ, Shyam, R, Horning, S, Sehn, LH, Farinha, P, Briones, J, Lossos, IS, Gascoyne, RD, Natkunam, Y
Publicada:
1 ene 2010
Resumen:
P>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 center dot 0028). Phosphorylated VEGFR2 (detected in 13% of cases) correlated with shorter progression-free survival (PFS, P = 0 center dot 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 center dot 036); in patients with weak VEGFR2, lack of VEGFR1 coexpression was significantly correlated with poor OS independent of IPI (P = 0 center dot 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.
Filiaciones:
Gratzinger, D:
Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA
Advani, R:
Stanford Univ, Sch Med, Dept Med, Div Oncol, Stanford, CA 94305 USA
Zhao, SC:
Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA
Talreja, N:
Stanford Univ, Sch Med, Dept Med, Div Oncol, Stanford, CA 94305 USA
Tibshirani, RJ:
Stanford Univ, Sch Med, Dept Hlth Res & Policy & Stat, Stanford, CA 94305 USA
Shyam, R:
Stanford Univ, Sch Med, Dept Hlth Res & Policy & Stat, Stanford, CA 94305 USA
Horning, S:
Stanford Univ, Sch Med, Dept Med, Div Oncol, Stanford, CA 94305 USA
Sehn, LH:
British Columbia Canc Agcy, Dept Pathol & Lab Med, Vancouver, BC V5Z 4E6, Canada
British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada
Univ British Columbia, Vancouver, BC V5Z 1M9, Canada
Farinha, P:
British Columbia Canc Agcy, Dept Pathol & Lab Med, Vancouver, BC V5Z 4E6, Canada
British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada
Univ British Columbia, Vancouver, BC V5Z 1M9, Canada
Briones, J:
Univ Autonoma Barcelona, Dept Clin Hematol, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
Lossos, IS:
Univ Miami, Dept Med, Div Haematol Oncol & Mol & Cellular Pharmacol, Sylvester Comprehens Canc Ctr, Miami, FL USA
Gascoyne, RD:
British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada
Univ British Columbia, Vancouver, BC V5Z 1M9, Canada
Natkunam, Y:
Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA
Green Accepted, Bronze
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