Originally published as JCO Early Release 10.1200/JCO.2006.10.0917 on May 29 2007

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HLA Class II Expression by Hodgkin Reed-Sternberg Cells Is an Independent Prognostic Factor in Classical Hodgkin's Lymphoma

Arjan Diepstra, Gustaaf W. van Imhoff, Henrike E. Karim-Kos, Anke van den Berg, Gerard J. te Meerman, Marijke Niens, Ilja M. Nolte, Esther Bastiaannet, Michael Schaapveld, Edo Vellenga, Sibrand Poppema

From the Departments of Pathology, Hematology, Genetics and Epidemiology, University Medical Center Groningen, University of Groningen; and the Comprehensive Cancer Center North Netherlands, Groningen, the Netherlands

Address reprint requests to Arjan Diepstra MD, Department of Pathology and Laboratory Medicine, University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, the Netherlands; e-mail: a.diepstra{at}path.umcg.nl

Purpose The neoplastic Hodgkin Reed-Sternberg (HRS) cells in classical Hodgkin's lymphoma (cHL) are derived from B cells. The frequency of HLA class II downregulation and its effect on prognosis are unknown.

Patients and Methods Immunohistochemistry results for HLA class II were evaluated in 292 primary cHL patients in a population-based approach. Patients were diagnosed between 1989 and 2000 in the northern part of the Netherlands. Median age at diagnosis was 38 years (range, 8 to 88 years); 63% had Ann Arbor stage I or II, 24% stage III, and 13% stage IV disease. Median follow-up was 7.1 years. For 168 patients, HLA genotype data were available.

Results Lack of HLA class II cell-surface expression on HRS cells was observed in 41.4% and was more common in patients with extranodal disease, patients with Epstein-Barr virus–negative disease, and patients with HLA class I–negative HRS cells. Alleles of three microsatellite markers in the HLA class II region were associated with presence or absence of protein expression. In univariate analyses, lack of HLA class II expression coincided with adverse outcome (5-years failure free survival [FFS], 67% v 85%; P = .001; 5-years age and sex matched relative survival (RS), 80% v 90%; P = .027). This effect remained in multivariate analyses for FFS with a hazard ratio of 2.40 (95% CI, 1.45 to 3.98) and RS with a relative excess risk of death of 2.55 (95% CI, 1.22 to 5.31).

Conclusion Lack of membranous HLA class II expression by HRS cells in diagnostic lymph node specimens is an independent adverse prognostic factor in cHL.

published online ahead of print at www.jco.org on May 29, 2007.

Supported by the Dutch Cancer Society (KWF Grant No. RUG 2000-2315) and the Dutch Organization of Scientific Research (NWO-MW Grant No. 920-03-136).

Presented at the 47th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 10-13, 2005.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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