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 & 2 others Dennis D. Weisenburger, Sophia S. Wang

Research output: Contribution to journalArticle

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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 immunohistochemistry-based markers on archival tissues.

Original languageEnglish (US)
Pages (from-to)245-252
Number of pages8
JournalInternational Journal of Molecular Epidemiology and Genetics
Volume2
Issue number3
StatePublished - Aug 30 2011

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Lymphoma, Large B-Cell, Diffuse
Epidemiologic Studies
Population
Rituximab
Germinal Center
Gene Expression Profiling
B-Cell Lymphoma
Fluorescence In Situ Hybridization
B-Lymphocytes
Immunohistochemistry
Staining and Labeling

Keywords

  • Diffuse large B-cell lymphoma
  • Germinal center
  • Immunohistochemistry
  • Molecular epidemiology

ASJC Scopus subject areas

  • Epidemiology
  • Genetics
  • Genetics(clinical)

Cite this

Immunostaining to identify molecular subtypes of diffuse large B-cell lymphoma in a population-based epidemiologic study in the pre-rituximab era. / Morton, Lindsay M.; Cerhan, James R.; Hartge, Patricia; Vasef, Mohammad A.; Neppalli, Vishala T.; Natkunam, Yasodha; Dogan, Ahmet; Dave, Bhavana J; Jain, Smrati; Levy, Ronald; Lossos, Izidore S.; Cozen, Wendy; Davis, Scott; Schenk, Mary Jean; Maurer, Matthew J.; Lynch, Charles F.; Rothman, Nathaniel; Chatterjee, Nilanjan; Yu, Kai; Staudt, Louis M.; Weisenburger, Dennis D.; Wang, Sophia S.

In: International Journal of Molecular Epidemiology and Genetics, Vol. 2, No. 3, 30.08.2011, p. 245-252.

Research output: Contribution to journalArticle

Morton, LM, Cerhan, JR, Hartge, P, Vasef, MA, Neppalli, VT, Natkunam, Y, Dogan, A, Dave, BJ, Jain, S, Levy, R, Lossos, IS, Cozen, W, Davis, S, Schenk, MJ, Maurer, MJ, Lynch, CF, Rothman, N, Chatterjee, N, Yu, K, Staudt, LM, Weisenburger, DD & Wang, SS 2011, 'Immunostaining to identify molecular subtypes of diffuse large B-cell lymphoma in a population-based epidemiologic study in the pre-rituximab era', International Journal of Molecular Epidemiology and Genetics, vol. 2, no. 3, pp. 245-252.
Morton, Lindsay M. ; Cerhan, James R. ; Hartge, Patricia ; Vasef, Mohammad A. ; Neppalli, Vishala T. ; Natkunam, Yasodha ; Dogan, Ahmet ; Dave, Bhavana J ; Jain, Smrati ; Levy, Ronald ; Lossos, Izidore S. ; Cozen, Wendy ; Davis, Scott ; Schenk, Mary Jean ; Maurer, Matthew J. ; Lynch, Charles F. ; Rothman, Nathaniel ; Chatterjee, Nilanjan ; Yu, Kai ; Staudt, Louis M. ; Weisenburger, Dennis D. ; Wang, Sophia S. / Immunostaining to identify molecular subtypes of diffuse large B-cell lymphoma in a population-based epidemiologic study in the pre-rituximab era. In: International Journal of Molecular Epidemiology and Genetics. 2011 ; Vol. 2, No. 3. pp. 245-252.
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AU - Morton, Lindsay M.

AU - Cerhan, James R.

AU - Hartge, Patricia

AU - Vasef, Mohammad A.

AU - Neppalli, Vishala T.

AU - Natkunam, Yasodha

AU - Dogan, Ahmet

AU - Dave, Bhavana J

AU - Jain, Smrati

AU - Levy, Ronald

AU - Lossos, Izidore S.

AU - Cozen, Wendy

AU - Davis, Scott

AU - Schenk, Mary Jean

AU - Maurer, Matthew J.

AU - Lynch, Charles F.

AU - Rothman, Nathaniel

AU - Chatterjee, Nilanjan

AU - Yu, Kai

AU - Staudt, Louis M.

AU - Weisenburger, Dennis D.

AU - Wang, Sophia S.

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N2 - 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 immunohistochemistry-based markers on archival tissues.

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