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Int J Mol Epidemiol Genet 2011;2(3):245-252

Original Article
Immunostaining to identify molecular subtypes of diffuse large B-cell
lymphoma in a population-based epidemiologic study in the pre-rituximab era

Lindsay M. Morton, James R. Cerhan, Patricia Hartge, Mohammad A. Vasef, Vishala T. Neppalli, Yasodha Natkunam, Ahmet
Dogan, Bhavana J. Dave, Smrati Jain, Ronald Levy, Izidore S. Lossos, Wendy Cozen, Scott Davis, Mary Jean Schenk, Matthew J.
Maurer, Charles F. Lynch, Nathaniel Rothman, Nilanjan Chatterjee, Kai Yu, Louis M. Staudt, Dennis D. Weisenburger, Sophia
S. Wang

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, MD, USA; Mayo Clinic College
of Medicine, Rochester, MN, USA; Department of Pathology, University of New Mexico, Albuquerque, NM, USA; Department of
Pathology, University of Iowa, Iowa City, IA, USA; Department of Pathology, Stanford University School of Medicine, Palo Alto, CA,
USA; University of Nebraska Medical Center, Omaha, NE, USA; Division of Oncology, Stanford University School of Medicine,
Palo Alto, CA, USA; Department of Medicine, Division of Hematology/Oncology, University of Miami/Sylvester Comprehensive
Cancer Center, Miami, FL, USA: Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Fred
Hutchinson Cancer Research Center and University of Washington, Seattle, WA, USA; Barbara Ann Karmanos Cancer Institute,
Wayne State University, Detroit, MI, USA: Department of Epidemiology, University of Iowa, Iowa City, IA, USA; Center for Cancer
Research, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA; Division of Etiology, Department of Population Sciences,
City of Hope, Duarte, CA, USA.

Received June 1, 2011; accepted June 12, 2011; Epub June 17, 2011; July, 2011

Abstract: Gene expression profiling studies have distinguished diffuse large B-cell lymphomas (DLBCLs) by cell of origin, with
distinct pathogenetic mechanisms and prognosis.  We attempted to identify DLBCL molecular subtypes in an epidemiologic
study of 214 DLBCL patients diagnosed during 1998-2000 with archival tissues to investigate etiology.  Immunohistochemical
staining for CD10, BCL6, LMO2, MUM1/IRF4, and BCL2 and fluorescence in situ hybridization for t(14;18) were conducted, with
≥93% blinded duplicate agreement.  CD10, LMO2, and BCL2 expression was similar to previous reports (32%, 44%, and 44%
of DLBCLs, respectively), but BCL6 and MUM1/IRF4 expression was lower than expected (29% and 5%, respectively).  We
classified 112/214 (52%) cases as germinal center B-cell–like DLBCL (GCB-DLBCL; Hans et al., Blood 2004; CD10+ or CD10-
/BCL6+/MUM1-), with no difference in prognosis compared with non-GCB-DLBCL (Cox regression, P=0.48).  Comparing other
GCB correlates, LMO2 expression and t(14;18) were more common but not exclusive to GCB-DLBCL as defined in our study,
whereas BCL2 expression did not differ between DLBCL molecular subtypes.  We could not confidently identify patients with
GCB-DLBCL using these IHC-based markers on archival tissues. (IJMEG1106001).

Key words: diffuse large B-cell lymphoma, germinal center, molecular epidemiology, immunohistochemistry

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Address all correspondence to:
Lindsay M. Morton, PhD
Division of Cancer Epidemiology and Genetics
National Cancer Institute, NIH, DHHS
6120 Executive Blvd., EPS 7040, MSC#7238
Rockville, MD 20852
Tel: 301-435-3972, Fax: 301-402-0207
E-mail: mortonli@mail.nih.gov