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Blood, 1 January 2004, Vol. 103, No. 1, pp. 275-282.
Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-05-1545.


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NEOPLASIA

Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray

Christine P. Hans, Dennis D. Weisenburger, Timothy C. Greiner, Randy D. Gascoyne, Jan Delabie, German Ott, H. Konrad Müller-Hermelink, Elias Campo, Rita M. Braziel, Elaine S. Jaffe, Zenggang Pan, Pedro Farinha, Lynette M. Smith, Brunangelo Falini, Alison H. Banham, Andreas Rosenwald, Louis M. Staudt, Joseph M. Connors, James O. Armitage, and Wing C. Chan

From the Departments of Pathology and Microbiology, Internal Medicine, and Preventive and Societal Medicine, University of Nebraska Medical Center, Omaha; Departments of Pathology and Medical Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada; Department of Pathology, Norwegian Radium Hospital, Oslo, Norway; Department of Pathology, University of Würzburg, Germany; Department of Pathology, Hospital Clinic, University of Barcelona, Spain; Southwest Oncology Group and Department of Pathology, University of Oregon Health Sciences Center, Portland; Hematopathology Section and Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; Institute of Hematology, University of Perugia, Italy; and Department of Clinical Laboratory Sciences, University of Oxford, United Kingdom.

Diffuse large B-cell lymphoma (DLBCL) can be divided into prognostically important subgroups with germinal center B-cell–like (GCB), activated B-cell–like (ABC), and type 3 gene expression profiles using a cDNA microarray. Tissue microarray (TMA) blocks were created from 152 cases of DLBCL, 142 of which had been successfully evaluated by cDNA microarray (75 GCB, 41 ABC, and 26 type 3). Sections were stained with antibodies to CD10, bcl-6, MUM1, FOXP1, cyclin D2, and bcl-2. Expression of bcl-6 (P < .001) or CD10 (P = .019) was associated with better overall survival (OS), whereas expression of MUM1 (P = .009) or cyclin D2 (P < .001) was associated with worse OS. Cases were subclassified using CD10, bcl-6, and MUM1 expression, and 64 cases (42%) were considered GCB and 88 cases (58%) non-GCB. The 5-year OS for the GCB group was 76% compared with only 34% for the non-GCB group (P < .001), which is similar to that reported using the cDNA microarray. Bcl-2 and cyclin D2 were adverse predictors in the non-GCB group. In multivariate analysis, a high International Prognostic Index score (3-5) and the non-GCB phenotype were independent adverse predictors (P < .0001). In summary, immunostains can be used to determine the GCB and non-GCB subtypes of DLBCL and predict survival similar to the cDNA microarray.


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