In Situ Hepatitis C NS3 Protein Detection Is Associated with High Grade Features in Hepatitis C-Associated B-Cell Non-Hodgkin Lymphomas
In Situ Hepatitis C NS3 Protein Detection Is Associated with High Grade Features in Hepatitis C-Associated B-Cell Non-Hodgkin Lymphomas
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DOI：
10.1371/journal.pone.0156384
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发表时间：
2016-06-03
期刊：
影响因子：
3.7
通讯作者：
Besson, Caroline
中科院分区：
文献类型：
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作者：
Canioni, Danielle;Michot, Jean-Marie;Besson, Caroline
丙型肝炎病毒 (HCV) 感染与 B 细胞非霍奇金淋巴瘤 (NHL)、优先边缘区淋巴瘤 (MZL) 和弥漫性大 B 细胞淋巴瘤 (DLBCL) 相关。虽然慢性抗原刺激是边缘区淋巴瘤 (MZL) 淋巴瘤发生的主要决定因素，但体外研究支持 B 细胞 HCV 感染的推定作用。我们在“ANRS HC-13 LymphoC”观察研究中进行了一项病理学研究，重点关注致癌 HCV 非结构 3 (NS3) 蛋白的原位表达。 Lympho-C研究纳入了116名HCV阳性的B-NHL患者，其中收集了86份组织学样本进行集中审查。主要组织学亚型是DLBCL（36%）和MZL（34%）。几乎一半的 DLBCL (12/26) 是由潜在的小 B 细胞淋巴瘤转化而来。 37 个测试样本中有 17 个 (46%) NS3 免疫染色呈阳性。 NS3 检测与高级淋巴瘤特征之间存在显着关联：14 例 DLBCL 中有 12 例为 NS3+，而 14 例 MZL 中只有 4 例为 NS3+（p = 0.006）。此外，4 个 NS3+ MZL 中有 2 个在大细胞中富集。值得注意的是，这项研究支持了一种新的转化机制，HCV 蛋白在高级别 B 淋巴瘤的发生中具有直接致癌作用。
Hepatitis C Virus (HCV) infection is associated with the B-cell non-Hodgkin lymphomas (NHL), preferentially marginal zone lymphomas (MZL) and diffuse large B-cell lymphomas (DLBCL). While chronic antigenic stimulation is a main determinant of lymphomagenesis in marginal zone lymphomas (MZL), a putative role of HCV infection of B-cells is supported by in vitro studies. We performed a pathological study within the "ANRS HC-13 LymphoC" observational study focusing on in situ expression of the oncogenic HCV non structural 3 (NS3) protein. Lympho-C study enrolled 116 HCV-positive patients with B-NHL of which 86 histological samples were collected for centralized review. Main histological subtypes were DLBCL (36%) and MZL (34%). Almost half of DLBCL (12/26) were transformed from underlying small B-cell lymphomas. NS3 immunostaining was found positive in 17 of 37 tested samples (46%). There was a striking association between NS3 detection and presence of high grade lymphoma features: 12 out of 14 DLBCL were NS3+ compared to only 4 out of 14 MZL (p = 0.006). Moreover, 2 among the 4 NS3+ MZL were enriched in large cells. Remarkably, this study supports a new mechanism of transformation with a direct oncogenic role of HCV proteins in the occurrence of high-grade B lymphomas.