TY - JOUR
T1 - Immunostaining to identify molecular subtypes of diffuse large B-cell lymphoma in a population-based epidemiologic study in the pre-rituximab era
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.
PY - 2011/8/30
Y1 - 2011/8/30
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.
AB - 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.
KW - Diffuse large B-cell lymphoma
KW - Germinal center
KW - Immunohistochemistry
KW - Molecular epidemiology
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M3 - Article
C2 - 21915363
AN - SCOPUS:80052607673
SN - 1948-1756
VL - 2
SP - 245
EP - 252
JO - International Journal of Molecular Epidemiology and Genetics
JF - International Journal of Molecular Epidemiology and Genetics
IS - 3
ER -