CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from the International DLBCL Rituximab-CHOP Consortium Program Study.
CD30, originally identified as a cell-surface marker of Reed-Sternberg and Hodgkin cells of classical Hodgkin lymphoma, is also expressed by several types of non-Hodgkin lymphoma, including a subset of diffuse large B-cell lymphoma (DLBCL). However, the prognostic and biological importance of CD30 expression in DLBCL is unknown. Here we report that CD30 expression is a favorable prognostic factor in a cohort of 903 de novo DLBCL patients. CD30 was expressed in ∼14% of DLBCL patients. Patients with CD30(+) DLBCL had superior 5-year overall survival (CD30(+), 79% vs CD30(-), 59%; P = .001) and progression-free survival (P = .003). The favorable outcome of CD30 expression was maintained in both the germinal center B-cell and activated B-cell subtypes. Gene expression profiling revealed the upregulation of genes encoding negative regulators of nuclear factor κB activation and lymphocyte survival, and downregulation of genes encoding B-cell receptor signaling and proliferation, as well as prominent cytokine and stromal signatures in CD30(+) DLBCL patients, suggesting a distinct molecular basis for its favorable outcome. Given the superior prognostic value, unique gene expression signature, and significant value of CD30 as a therapeutic target for brentuximab vedotin in ongoing successful clinical trials, it seems appropriate to consider CD30(+) DLBCL as a distinct subgroup of DLBCL.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Shimin
S
Hu
Zijun Y
ZY
Xu-Monette
Aarthi
A
Balasubramanyam
Ganiraju C
GC
Manyam
Carlo
C
Visco
Alexander
A
Tzankov
Wei-min
WM
Liu
Roberto N
RN
Miranda
Li
L
Zhang
Santiago
S
Montes-Moreno
Karen
K
Dybkær
April
A
Chiu
Attilio
A
Orazi
Youli
Y
Zu
Govind
G
Bhagat
Kristy L
KL
Richards
Eric D
ED
Hsi
William W L
WW
Choi
J
J
Han van Krieken
Qin
Q
Huang
Jooryung
J
Huh
Weiyun
W
Ai
Maurilio
M
Ponzoni
Andrés J M
AJ
Ferreri
Xiaoying
X
Zhao
Jane N
JN
Winter
Mingzhi
M
Zhang
Ling
L
Li
Michael B
MB
Møller
Miguel A
MA
Piris
Yong
Y
Li
Ronald S
RS
Go
Lin
L
Wu
L Jeffrey
LJ
Medeiros
Ken H
KH
Young
D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D017730:Ki-1 Antigen / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D000069283:Rituximab; D016019:Survival Analysis; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D017730:Ki-1 Antigen; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone