BCL2 Predicts Survival in Germinal Center B-cell-like Diffuse Large B-cell Lymphoma Treated with CHOP-like Therapy and Rituximab

被引：142

作者：

Iqbal, Javeed ^{[1
]}

Meyer, Paul N. ^{[1
]}

Smith, Lynette M. ^{[3
]}

Johnson, Nathalie A. ^{[4
]}

Vose, Julie M. ^{[2
]}

Greiner, Timothy C. ^{[1
]}

Connors, Joseph M. ^{[4
]}

Staudt, Louis M. ^{[5
]}

Rimsza, Lisa ^{[7
]}

Jaffe, Elaine ^{[6
]}

Rosenwald, Andreas ^{[8
]}

Ott, German ^{[9
,10
]}

Delabie, Jan ^{[11
]}

Campo, Elias ^{[12
]}

Braziel, Rita M. ^{[13
]}

Cook, James R. ^{[14
]}

Tubbs, Raymond R. ^{[14
]}

Gascoyne, Randy D. ^{[4
]}

Armitage, James O. ^{[2
]}

Weisenburger, Dennis D. ^{[1
]}

Chan, Wing C. ^{[1
]}

机构：

[1] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA

[2] Univ Nebraska Med Ctr, Dept Hematol Oncol, Omaha, NE USA

[3] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Biostat, Omaha, NE USA

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

[5] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[6] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[7] Univ Arizona, Dept Pathol, Tucson, AZ USA

[8] Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany

[9] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Baden Wurttembe, Germany

[10] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Baden Wurttembe, Germany

[11] Univ Oslo, Norwegian Radium Hosp, Dept Pathol, Oslo, Norway

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

[13] Oregon Hlth, Clin Pathol, Portland, OR USA

[14] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44106 USA

来源：

CLINICAL CANCER RESEARCH | 2011年 / 17卷 / 24期

关键词：

NON-HODGKINS-LYMPHOMA; PROGNOSTIC-SIGNIFICANCE; PROTEIN EXPRESSION; ELDERLY-PATIENTS; R-CHOP; IMMUNOHISTOCHEMICAL BIOMARKERS; BCL-2-ASSOCIATED RESISTANCE; CLINICAL-SIGNIFICANCE; MYC REARRANGEMENTS; MOLECULAR SUBTYPES;

D O I：

10.1158/1078-0432.CCR-11-0267

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: We have previously shown the prognostic significance of BCL2 expression in the activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) patients treated with cyclophosphamide-Adriamycin-vincristine- prednisone (CHOP) or CHOP-like therapy. However, after the inclusion of rituximab (R) in the CHOP regimen, several conflicting observations about the prognostic value of BCL2 expression have been reported. Experimental Design: We evaluated the R-CHOP cohort of 221 DLBCL cases with gene expression profiling data. BCL2 protein (n = 169), mRNA(n = 221) expression, and t(14; 18) (n = 144) were correlated with clinical outcome. The CHOP cohort (n = 181) was used for comparative analysis. Results: BCL2 protein expression has significant impact on overall survival (OS) and event-free survival (EFS) in DLBCL (OS, P = 0.009; EFS, P = 0.001) and GCB-DLBCL (OS, P = 0.03; EFS, P = 0.002) but not in ABC-DLBCL in the R-CHOP cohort. The survival differences for EFS in GCB-DLBCL were still observed in multivariate analysis. At the mRNA level, this correlation was observed in EFS in DLBCL (P = 0.006), but only a trend was observed in GCB-DLBCL (P = 0.09). The t(14; 18) was detected in 34% of GCB-DLBCL but was not associated with significant differences in survival. Gene enrichment analysis identified significant enrichment of the DLBCL "stromal-1" signatures and hypoxia-inducible factor 1 (HIF1-alpha) signature in BCL2 (-)GCB-DLBCL, whereas T-FH cell signatures were enriched in BCL2(+) GCB-DLBCL. Conclusion: The prognostic significance of BCL2 has changed after inclusion of rituximab in the treatment protocol and is observed in the GCB-DLBCL rather than the ABC-DLBCL. Although rituximab has benefited patients in both DLBCL subgroups, the BCL2(+) GCB-DLBCL seems to receive less benefit from this treatment and may require other novel therapeutic intervention. Clin Cancer Res; 17(24); 7785-95. (C) 2011 AACR.

引用

页码：7785 / 7795

页数：11

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