Abstract
A proportion of classical Hodgkin lymphomas harbor the Epstein Barr virus (EBV). We previously demonstrated that associations between Human Leukocyte Antigen (HLA) alleles and susceptibility to EBV+ classical Hodgkin lymphoma differ between European and Chinese populations. Data on Hispanic populations is missing. Here we examined the association between HLA type, tumor cell HLA expression and other characteristics in Hispanic Hodgkin lymphoma patients. Hispanic Hodgkin lymphoma patients diagnosed at the Los Angeles County-University of Southern California Medical Center from 2000–2012 were included (n = 65). Formalin-fixed paraffin-embedded tumor tissue was analyzed for EBV by in situ hybridization and for HLA class I and class II expression by immunohistochemistry. HLA typing was performed by HLA-A specific quantitative PCR of genomic DNA from tissue. Thirty patients (46%) had EBV+ tumors. Expression of HLA class I (p = 0.0006) was significantly associated with EBV+ tumor status in Hispanic patients, similar to Europeans and Chinese. A positive association between HLA class II expression and EBV+ tumor status, as present in large studies in Europeans, was not found (p = 0.06). The prevalences of the specific European HLA-A*01 risk and European HLA-A*02 protective types were not significantly associated with EBV+ tumors among these Hispanic patients, however numbers were too low to draw firm conclusions. The HLA-A*02:07 allele, that is associated with EBV+ Hodgkin lymphoma in Chinese, was absent. In conclusion, the association between EBV positivity in tumor cells and HLA class I expression appears to be consistent across different populations. Larger studies in Hispanics are needed to evaluate HLA allele susceptibility associations.
Highlights
Classical Hodgkin lymphoma is a malignant lymphoma of B cell origin defined by a pathognomonic giant malignant cell, the Hodgkin Reed-Sternberg (HRS) cell
human leukocyte antigens (HLA) class I expression was positively associated with Epstein Barr Virus (EBV)+ Classical Hodgkin lymphoma (cHL) (p = 0.0006) (Table 3)
EBV+ tumor cell status was significantly associated with HLA class I expression when adjusting for histology (Table 4, OR = 6.53, 95%CI = 1.80–23.72)
Summary
Classical Hodgkin lymphoma (cHL) is a malignant lymphoma of B cell origin defined by a pathognomonic giant malignant cell, the Hodgkin Reed-Sternberg (HRS) cell It comprises 11% of malignant lymphomas and is the most common lymphoma of young adults. Epstein-Barr Virus (EBV) has been shown to be clonally integrated in the malignant HRS cells in about 40% of cHL patients overall and ~20% of young adult nodular sclerosis cases (EBV+ cases) [1]. The presentation of peptides derived from these EBV proteins is mediated through human leukocyte antigens (HLA) classes I and/or II Both cytotoxic T cells that recognize HLA class I [9,10] and T helper cells that react to HLA class II are involved in the antitumor immune response against EBV [11]. GWAS studies have shown that the HLA-A gene region is the dominant genetic susceptibility risk factor for EBV+ cHL, while loci in the class II region (HLA-DRA) are associated with EBV- cHL and NS cHL [15,16,17]
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