HLA Class I and EBV Positive Classical Hodgkin Lymphoma In the Chinese Population

Abstract 2688

In Caucasian populations, the tumor cells of Epstein Barr virus (EBV)-positive classical Hodgkin Lymphomas (cHL) patients more frequently express HLA class I and HLA class II molecules compared to EBV-negative cHL patients. Since HRS cells also express other components of the antigen presenting pathway it can be anticipated that HRS cells in EBV-positive cHL should be able to present EBV derived antigenic peptides. In on our previous genotyping study we demonstrated that the HLA-A*02 allele was associated with a reduced and the HLA-A*01 allele with an increased risk of developing EBV-positive cHL. Intuitively, this can be explained by the generally acknowledged lack of HLA-A*01 restricted immune responses to latent EBV peptides. In this study, we analyzed HLA class I expression and the HLA association in relation to EBV in Asian cHL patients.

Formalin-fixed and paraffin embedded (FFPE) tissue blocks were available for 145 cHL patients and from 79 controls from 5 hospitals from the Northern part of China. Hematoxylin & Eosin-stained sections were used to reclassify the histological subtypes according to the WHO classification. EBV status was determined by EBER in situ hybridization. Membranous expression of HLA class I was detected by immunohistochemistry using antibodies against HLA class I (HC-10) and ß2-microglobulin. DNA was isolated from FFPE samples to detect the HLA-A*02 allele by quantitative PCR. 23 cHL cases and 5 controls were excluded due to poor DNA quality.

Positive EBV status was observed in 40% (58/145) of the Chinese cHL patients. As expected, the percentage of EBV-positive cases was much higher in the mixed cellularity subtype (71%) than in the nodular sclerosis subtype (16%; p<0.001). Expression of HLA class I was observed in 79% of the EBV-positive cHL patients and in 30% of the EBV-negative patients (p<0.001) consistent with the previous findings in the Dutch population. The HLA-A*02 allele was detected in 71% of the EBV-positive cHL and in 64% of the EBV-negative cHL patients (NS). In the controls HLA-A*02 was observed in 67% of the cases.

In this Chinese population, the tumor cells of EBV-positive cHL more frequently retained membranous HLA class I expression, similar to the Caucasian populations. The inverse correlation between presence of the HLA-A*02 allele and positive EBV status, as observed in Caucasians, is not present in these northern Chinese cHL patients. Differences in ethnic background might explain discrepancies in HLA-A association with EBV-positive cHL in different populations.