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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 Outcome¹

Departments of Lymphoma and Myeloma [M. H., K-O. K., F. C., A. H. S.] and Hematopathology [M. H., G. Z. R., L. J. M.], University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030; Departments of Medical Oncology [S. V., V. B., A. M. G., G. B.] and Pathology [R. G.], Istituto Tumori, Milan, Italy; Departments of Hematology [G. N., G. P.] and Pathology [M. C.], University of Verona, Verona, Italy; and First Department of Internal Medicine [T. P. V., G. A. P.] and Laboratory of Histology and Embryology [C. K.], National and Kapodistrian University of Athens, Athens, Greece

Purpose: 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.

Experimental Design: 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.

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