Loss of major histocompatibility class II gene and protein expression in primary mediastinal large B-cell lymphoma is highly coordinated and related to poor patient survival.
Loss of major histocompatibility class II (MHC II) expression in diffuse large B-cell lymphoma (DLBCL) correlates with worse outcome, possibly from decreased immunosurveillance. Primary mediastinal B-cell lymphoma (PMBCL) is a subtype of DLBCL which reportedly has frequent loss of MHC II proteins; however, PM-BCL has better survival than DLBCL. To investigate this paradox, we used geneexpression profiling (GEP) data and immunohistochemistry to study expression of MHC II and its regulatory genes and to determine their relationship to PMBCL survival. We found that GEP levels correlated between MHC II genes and the transcriptional regulator MHC2TA but not other adjacent genes, implying that transcriptional regulation of MHC II in PMBCL was intact and that MHC II gene deletion was unlikely. MHC II average expression was lower than in certain subtypes of DLBCL; however, only 12% had complete loss of MHC II expression. Poor patient survival in PMBCL correlated with incremental decreases in MHC II expression. Although overall survival was better, survival of the lowest 10% of MHC II expressers was similarly poor in DLBCL and PMBCL. MHC II expression may define a therapeutic target in both these diseases.
Department of Pathology, University of Arizona, Tucson, AZ 85724-5043, USA.
Robin A
RA
Roberts
George
G
Wright
Andreas R
AR
Rosenwald
Marina A
MA
Jaramillo
Thomas M
TM
Grogan
Thomas P
TP
Miller
Yvette
Y
Frutiger
Wing C
WC
Chan
Randy D
RD
Gascoyne
German
G
Ott
H Konrad
HK
Muller-Hermelink
Louis M
LM
Staudt
Lisa M
LM
Rimsza
D004247:DNA / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology; D008479:Mediastinal Neoplasms / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D015996:Survival Rate; D015534:Trans-Activators / Q000235:genetics*; D016896:Treatment Outcome
D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D004247:DNA