Expression of Epstein-Barr virus latent membrane protein-1 in Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma: associations with presenting features, serum interleukin 10 levels, and clinical outcome.
OBJECTIVE
EBV-latent membrane protein-1 (LMP-1) is often expressed in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin's lymphoma (cHL), but its clinical significance is controversial. We correlated LMP-1 with presenting features, including serum interleukin 10 levels and clinical outcome.


METHODS
Patients were eligible if they had biopsy-proven cHL, were untreated, HIV-1 negative, and had available archival tissue. LMP-1 expression was determined by immunohistochemistry.


RESULTS
We identified 577 patients with cHL with a median age of 30 years, 55% of whom were male. LMP-1 was expressed in HRS cells of 124 patients (21%) and was detected in 78 of 461 (17%) patients with nodular sclerosis compared with 44 of 112 (39%) with mixed cellularity (P < 0.001 by Fisher's exact test). Patients with tumors with LMP-1-positive HRS cells had higher serum interleukin 10 levels (P = 0.009 by Mann-Whitney test). For the 303 patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalent regimens, the 5-year failure-free survival (FFS) for those with LMP-1-positive tumors was 74% compared with 81% for those with LMP-1-negative tumors (P = 0.23, by log-rank test). Overall survival (OS) at 5 years for patients with LMP-1-positive tumors was 90 versus 91% for patients with LMP-1-negative tumors (P = 0.8 by log-rank test). Expression of LMP-1 was not associated with different FFS and OS in patients treated with other regimens or with radiotherapy alone.


CONCLUSIONS
LMP-1 was expressed by HRS cells in 21% of cHL and correlated with mixed cellularity type and higher serum interleukin 10 levels. The presence of LMP-1 was not associated with FFS or OS in uniformly treated patients.
Herling
Marco
M
Department of Lymphoma and Myeloma, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Rassidakis
George Z
GZ
Medeiros
L Jeffrey
LJ
Vassilakopoulos
Theodoros P
TP
Kliche
Kay-Oliver
KO
Nadali
Gianpaolo
G
Viviani
Simonetta
S
Bonfante
Valeria
V
Giardini
Roberto
R
Chilosi
Marco
M
Kittas
Christos
C
Gianni
Alessandro M
AM
Bonadonna
Gianni
G
Pizzolo
Giovanni
G
Pangalis
Gerassimos A
GA
Cabanillas
Fernando
F
Sarris
Andreas H
AH
D000328:Adult; D000368:Aged; D005260:Female; D006689:Hodgkin Disease / Q000097:blood / Q000401:mortality / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016539:Reed-Sternberg Cells / Q000821:virology*; D014763:Viral Matrix Proteins / Q000032:analysis*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D016753:Interleukin-10