High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy

被引：94

作者：

Cardesa-Salzmann, Teresa M. ^{[1
]}

Colomo, Luis ^{[1
]}

Gutierrez, Gonzalo ^{[1
]}

Chan, Wing C. ^{[2
]}

Weisenburger, Dennis ^{[2
]}

Climent, Fina ^{[3
]}

Gonzalez-Barca, Eva ^{[4
]}

Mercadal, Santiago ^{[4
]}

Arenillas, Leonor ^{[5
]}

Serrano, Sergio ^{[5
]}

Tubbs, Ray ^{[6
]}

Delabie, Jan ^{[7
]}

Gascoyne, Randy D. ^{[8
]}

Connors, Joseph M. ^{[8
]}

Mate, Jose L. ^{[9
]}

Rimsza, Lisa ^{[10
]}

Braziel, Rita ^{[11
]}

Rosenwald, Andreas ^{[12
]}

Lenz, Georg ^{[13
]}

Wright, George ^{[14
]}

Jaffe, Elaine S. ^{[14
]}

Staudt, Louis ^{[14
]}

Jares, Pedro ^{[1
]}

Lopez-Guillermo, Armando ^{[1
]}

Campo, Elias ^{[1
]}

机构：

[1] Univ Barcelona, Hosp Clin, Barcelona, Spain

[2] Univ Nebraska Med Ctr, Omaha, NE USA

[3] Hosp Univ Bellvitge, Lhospitalet De Llobregat, Spain

[4] Hosp Duran i Reynals, Inst Catala Oncol, Lhospitalet De Llobregat, Spain

[5] Hosp del Mar, Barcelona, Spain

[6] Cleveland Clin, Cleveland, OH 44106 USA

[7] Norwegian Radium Hosp, Oslo, Norway

[8] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada

[9] Hosp Germans Trias, Badalona, Spain

[10] Univ Arizona, Ctr Canc, Tucson, AZ USA

[11] Oregon Hlth & Sci Univ, Portland, OR USA

[12] Univ Wurzburg, Wurzburg, Germany

[13] Mol Krebsforschungszentrum MKFZ Charite Univ Med, Berlin, Germany

[14] NCI, NIH, Bethesda, MD 20892 USA

来源：

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL | 2011年 / 96卷 / 07期

关键词：

rituximab; aggressive non-Hodgkin's lymphoma; kidney; central nervous system; NF-KAPPA-B; PROGNOSTIC-SIGNIFICANCE; FOLLICULAR LYMPHOMA; GENE SIGNATURES; VEGF-A; SURVIVAL; ANGIOGENESIS; EXPRESSION; IMMUNOCHEMOTHERAPY; MUTATIONS;

D O I：

10.3324/haematol.2010.037408

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Diffuse large B-cell lymphoma is a clinically and molecularly heterogeneous disease. Gene expression profiling studies have shown that the tumor microenvironment affects survival and that the angiogenesis-related signature is prognostically unfavorable. The contribution of histopathological microvessel density to survival in diffuse large B-cell lymphomas treated with immunochemotherapy remains unknown. The purpose of this study is to assess the prognostic impact of histopathological microvessel density in two independent series of patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Design and Methods One hundred and forty-seven patients from the Leukemia Lymphoma Molecular Profiling Project (training series) and 118 patients from the Catalan Lymphoma-Study group-GELCAB (validation cohort) were included in the study. Microvessels were immunostained with CD31 and quantified with a computerized image analysis system. The stromal scores previously defined in 110 Leukemia Lymphoma Molecular Profiling Project cases were used to analyze correlations with microvessel density data. Results Microvessel density significantly correlated with the stromal score (r = 0.3209; P < 0.001). Patients with high microvessel density showed significantly poorer overall survival than those with low microvessel density both in the training series (4-year OS 54% vs. 78%; P = 0.004) and in the validation cohort (57% vs. 81%; P = 0.006). In multivariate analysis, in both groups high microvessel density was a statistically significant unfavorable prognostic factor independent of international prognostic index [training series: international prognostic index (relative risk 2.7; P = 0.003); microvessel density (relative risk 1.96; P = 0.002); validation cohort: international prognostic index (relative risk 4.74; P < 0.001); microvessel density (relative risk 2.4; P = 0.016)]. Conclusions These findings highlight the impact of angiogenesis in the outcome of patients with diffuse large B-cell lymphoma and the interest of evaluating antiangiogenic drugs in clinical trials.

引用

页码：996 / 1001

页数：6

共 30 条

[1] Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling [J].

Alizadeh, AA ;

Eisen, MB ;

Davis, RE ;

Ma, C ;

Lossos, IS ;

Rosenwald, A ;

Boldrick, JG ;

Sabet, H ;

Tran, T ;

Yu, X ;

Powell, JI ;

Yang, LM ;

Marti, GE ;

Moore, T ;

Hudson, J ;

Lu, LS ;

Lewis, DB ;

Tibshirani, R ;

Sherlock, G ;

Chan, WC ;

Greiner, TC ;

Weisenburger, DD ;

Armitage, JO ;

Warnke, R ;

Levy, R ;

Wilson, W ;

Grever, MR ;

Byrd, JC ;

Botstein, D ;

Brown, PO ;

Staudt, LM .

NATURE, 2000, 403 (6769) :503-511

[2] Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction [J].

Bea, S ;

Zettl, A ;

Wright, G ;

Salaverria, I ;

Jehn, P ;

Moreno, V ;

Burek, C ;

Ott, G ;

Puig, X ;

Yang, LM ;

Lopez-Guillermo, A ;

Chan, WC ;

Greiner, TC ;

Weisenburger, DD ;

Armitage, JO ;

Gascoyne, RD ;

Connors, JM ;

Grogan, TM ;

Braziel, R ;

Fisher, RI ;

Smeland, EB ;

Kvaloy, S ;

Holte, H ;

Delabie, J ;

Simon, R ;

Powell, J ;

Wilson, WH ;

Jaffe, ES ;

Montserrat, E ;

Muller-Hermelink, HK ;

Staudt, LM ;

Campo, E ;

Rosenwald, A .

BLOOD, 2005, 106 (09) :3183-3190

[3] Revised response criteria for malignant lymphoma [J].

Cheson, Bruce D. ;

Pfistner, Beate ;

Juweid, Malik E. ;

Gascoyne, Randy D. ;

Specht, Lena ;

Horning, Sandra J. ;

Coiffier, Bertrand ;

Fisher, Richard I. ;

Hagenbeek, Anton ;

Zucca, Emanuele ;

Rosen, Steven T. ;

Stroobants, Sigrid ;

Lister, T. Andrew ;

Hoppe, Richard T. ;

Dreyling, Martin ;

Tobinai, Kensei ;

Vose, Julie M. ;

Connors, Joseph M. ;

Federico, Massimo ;

Diehl, Volker .

JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (05) :579-586

[4] CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. [J].

Coiffier, B ;

Lepage, E ;

Brière, J ;

Herbrecht, R ;

Tilly, H ;

Bouabdallah, R ;

Morel, P ;

Van den Neste, E ;

Salles, G ;

Gaulard, P ;

Reyes, F ;

Gisselbrecht, C .

NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (04) :235-242

[5] Mutations of multiple genes cause deregulation of NF-κB in diffuse large B-cell lymphoma [J].

Compagno, Mara ;

Lim, Wei Keat ;

Grunn, Adina ;

Nandula, Subhadra V. ;

Brahmachary, Manisha ;

Shen, Qiong ;

Bertoni, Francesco ;

Ponzoni, Maurilio ;

Scandurra, Marta ;

Califano, Andrea ;

Bhagat, Govind ;

Chadburn, Amy ;

Dalla-Favera, Riccardo ;

Pasqualucci, Laura .

NATURE, 2009, 459 (7247) :717-U124

[6] Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma [J].

Davis, R. Eric ;

Ngo, Vu N. ;

Lenz, Georg ;

Tolar, Pavel ;

Young, Ryan M. ;

Romesser, Paul B. ;

Kohlhammer, Holger ;

Lamy, Laurence ;

Zhao, Hong ;

Yang, Yandan ;

Xu, Weihong ;

Shaffer, Arthur L. ;

Wright, George ;

Xiao, Wenming ;

Powell, John ;

Jiang, Jian-Kang ;

Thomas, Craig J. ;

Rosenwald, Andreas ;

Ott, German ;

Muller-Hermelink, Hans Konrad ;

Gascoyne, Randy D. ;

Connors, Joseph M. ;

Johnson, Nathalie A. ;

Rimsza, Lisa M. ;

Campo, Elias ;

Jaffe, Elaine S. ;

Wilson, Wyndham H. ;

Delabie, Jan ;

Smeland, Erlend B. ;

Fisher, Richard I. ;

Braziel, Rita M. ;

Tubbs, Raymond R. ;

Cook, J. R. ;

Weisenburger, Dennis D. ;

Chan, Wing C. ;

Pierce, Susan K. ;

Staudt, Louis M. .

NATURE, 2010, 463 (7277) :88-U97

[7] Constitutive nuclear factor κB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells [J].

Davis, RE ;

Brown, KD ;

Siebenlist, U ;

Staudt, LM .

JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 194 (12) :1861-1874

[8] VEGF-targeted therapy: mechanisms of anti-tumour activity [J].

Ellis, Lee M. ;

Hicklin, Daniel J. .

NATURE REVIEWS CANCER, 2008, 8 (08) :579-591

[9] Vascularization predicts overall survival and risk of transformation in follicular lymphoma [J].

Farinha, Pedro ;

Kyle, Alastair H. ;

Minchinton, Andrew I. ;

Connors, Joseph M. ;

Karsan, Aly ;

Gascoyne, Randy D. .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2010, 95 (12) :2157-2160

[10] NFκB activity, function, and target-gene signatures in primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma subtypes [J].

Feuerhake, F ;

Kutok, JL ;

Monti, S ;

Chen, W ;

LaCasce, AS ;

Cattoretti, G ;

Kurtin, P ;

Pinkus, GS ;

de Leval, L ;

Harris, NL ;

Savage, KJ ;

Neuberg, D ;

Habermann, TM ;

Dalla-Favera, R ;

Golub, TR ;

Aster, JC ;

Shipp, MA .

BLOOD, 2005, 106 (04) :1392-1399

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