Deng Lijuan, Song Yuqin, Young Ken H, Hu Shimin, Ding Ning, Song Weiwei, Li Xianghong, Shi Yunfei, Huang Huiying, Liu Weiping, Zheng Wen, Wang Xiaopei, Xie Yan, Lin Ningjing, Tu Meifeng, Ping Lingyan, Ying Zhitao, Zhang Chen, Sun Yingli, Zhu Jun
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Lymphoma Unit, Peking University Cancer Hospital & Institute, Beijing, China.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Oncotarget. 2015 Sep 22;6(28):25061-73. doi: 10.18632/oncotarget.4677.
While the epidemiologic association between hepatitis B virus (HBV) infection and diffuse large B-cell lymphoma (DLBCL) is established, little is known more than this epidemiologic evidence. We studied a cohort of 587 patients with DLBCL for HBV infection status, clinicopathologic features, and the immunoglobulin variable region in HBV surface antigen (HBsAg)-positive patients. Eighty-one (81/587, 13.8%) patients were HBsAg-positive. Compared with HBsAg-negative DLBCL, HBsAg-positive DLBCL displayed a younger median onset age (45 vs. 55 years), more frequent involvement of spleen or retroperitoneal lymph node (40.7% vs. 16.0% and 61.7% vs. 31.0% respectively, both p < 0.001), more advanced disease (stage III/IV: 76.5% vs 59.5%, p = 0.003), and significantly worse outcome (2-year overall survival: 47% versus 70%, p < 0.001). In HBsAg-positive DLBCL patients, almost all (45/47, 96%) amino acid sequences of heavy and light chain complementarity determining region 3 exhibited a high homology to antibodies specific for HBsAg, and the majority (45/50, 90%) of IgHV and IgLV genes were mutated. We conclude that 13.8% of DLBCL cases are HBV-associated in HBV-endemic China and show unique clinical features and poor outcomes. Furthermore, our study strongly suggests that HBV-associated DLBCL might arise from HBV antigen-selected B cells.
虽然乙型肝炎病毒（HBV）感染与弥漫性大B细胞淋巴瘤（DLBCL）之间的流行病学关联已得到证实，但除了这一流行病学证据外，人们对此了解甚少。我们研究了一组587例DLBCL患者的HBV感染状况、临床病理特征以及HBsAg阳性患者的免疫球蛋白可变区。81例（81/587，13.8%）患者HBsAg阳性。与HBsAg阴性的DLBCL相比，HBsAg阳性的DLBCL发病年龄中位数更年轻（45岁对55岁），脾脏或腹膜后淋巴结受累更频繁（分别为40.7%对16.0%和61.7%对31.0%，均p<0.001），疾病分期更晚（III/IV期：76.5%对59.5%，p = 0.003），预后明显更差（2年总生存率：47%对70%，p<0.001）。在HBsAg阳性的DLBCL患者中，重链和轻链互补决定区3的几乎所有氨基酸序列（45/47，96%）与HBsAg特异性抗体具有高度同源性，并且大多数（45/50，90%）的IgHV和IgLV基因发生了突变。我们得出结论，在HBV流行的中国，13.8%的DLBCL病例与HBV相关，具有独特的临床特征和较差的预后。此外，我们的研究强烈表明，HBV相关的DLBCL可能起源于HBV抗原选择的B细胞。
