Division of Hematology, Department of Internal Medicine, Medical University Graz, Graz, Austria.
Mod Pathol. 2013 Feb;26(2):182-94. doi: 10.1038/modpathol.2012.134. Epub 2012 Aug 31.
Chemokine receptors have a crucial role in the development and progression of lymphoid neoplasms. To determine the chemokine receptor expression profile in gastric mucosa-associated lymphoid tissue (MALT) lymphoma, we performed an expression analysis of 19 chemokine receptors at mRNA levels by using real-time RT-PCR, as well as of five chemokine receptors--CCR8, CCR9, CXCR4, CXCR6 and CXCR7--by immunohistochemistry on human tissue samples of Helicobacter pylori-associated gastritis, gastric MALT lymphoma and gastric extranodal diffuse large B-cell lymphoma originating from MALT lymphoma (transformed MALT lymphoma). Following malignant transformation from H. pylori-associated gastritis to MALT lymphoma, an upregulation of CCR7, CXCR3 and CXCR7, and a loss of CXCR4 were detected. The transformation of gastric MALT lymphomas to gastric extranodal diffuse large B-cell lymphoma was accompanied by upregulation of CCR1, CCR5, CCR7, CCR8, CCR9, CXCR3, CXCR6, CXCR7 and XCR1. Remarkably, CXCR4 expression was exclusively found in nodal marginal B-cell lymphomas and nodal diffuse large B-cell lymphomas but not at extranodal manifestation sites, ie, in gastric MALT lymphomas or gastric extranodal diffuse large B-cell lymphomas. Furthermore, the incidence of bone marrow infiltration (16/51 with bone marrow involvement vs 35/51 with bone marrow involvement; Spearman ρ=0467 P<0.001) positively correlated with CXCR4 expression. CXCL12, the ligand of CXCR4 and CXCR7, was expressed by epithelial, endothelial and inflammatory cells, MALT lymphoma cells and was most strongly expressed by extranodal diffuse large B-cell lymphoma cells, suggesting at least in part an autocrine signaling pathway. Our data indicate that CXCR4 expression is associated with nodal manifestation and a more advanced stage of lymphomas and hence, might serve as useful clinical prognostic marker.
趋化因子受体在淋巴肿瘤的发生和发展中起着至关重要的作用。为了确定胃黏膜相关淋巴组织（MALT）淋巴瘤中趋化因子受体的表达谱，我们通过实时 RT-PCR 检测了 19 种趋化因子受体的 mRNA 水平，并通过免疫组织化学检测了 5 种趋化因子受体——CCR8、CCR9、CXCR4、CXCR6 和 CXCR7——在幽门螺杆菌相关胃炎、胃 MALT 淋巴瘤和源自 MALT 淋巴瘤的胃结外弥漫性大 B 细胞淋巴瘤（转化型 MALT 淋巴瘤）的人类组织样本上的表达。从幽门螺杆菌相关胃炎恶性转化为 MALT 淋巴瘤后，检测到 CCR7、CXCR3 和 CXCR7 的上调，以及 CXCR4 的丢失。胃 MALT 淋巴瘤向胃结外弥漫性大 B 细胞淋巴瘤的转化伴随着 CCR1、CCR5、CCR7、CCR8、CCR9、CXCR3、CXCR6、CXCR7 和 XCR1 的上调。值得注意的是，CXCR4 表达仅在结内边缘 B 细胞淋巴瘤和结内弥漫性大 B 细胞淋巴瘤中发现，而不在结外表现部位，即胃 MALT 淋巴瘤或胃结外弥漫性大 B 细胞淋巴瘤中发现。此外，骨髓浸润的发生率（有骨髓浸润的 16/51 例与有骨髓浸润的 35/51 例；Spearman ρ=0.467，P<0.001）与 CXCR4 表达呈正相关。CXCR4 和 CXCR7 的配体 CXCL12 由上皮细胞、内皮细胞和炎症细胞、MALT 淋巴瘤细胞表达，并且在结外弥漫性大 B 细胞淋巴瘤细胞中表达最强，这至少部分表明存在自分泌信号通路。我们的数据表明，CXCR4 表达与结内表现和淋巴瘤的更晚期阶段相关，因此可能作为有用的临床预后标志物。
