Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People's Republic of China; Division of Hematology.
Division of Hematology.
Am J Med Sci. 2019 Apr;357(4):302-310. doi: 10.1016/j.amjms.2019.01.008. Epub 2019 Jan 21.
A few studies have evaluated the expression of chemokine receptors CXCR4 and CCR7 in diffuse large B-cell lymphoma (DLBCL); however, the association between CXCR4 and CCR7 with bone marrow (BM) involvement and their synergistic effect on prognosis is still unclear. Our study investigated this aspect.
Specimens were obtained from 61 primary nodal DLBCL patients and 100 reactive proliferative lymphadenitis patients. CXCR4 and CCR7 expression levels were examined by immunohistochemical staining; the relationship between these levels and clinical parameters and the differences in overall survival were analyzed.
CXCR4 and CCR7 overexpression was observed in the malignant lymph node tissues from most DLBCL patients. CCR7 expression was significantly higher in the non-GCB than the GCB subtype; CXCR4 positivity rates showed no significant difference between the 2 subtypes. In DLBCL patients with BM involvement, CXCR4 was overexpressed in almost all BM samples, but CCR7 expression was low in BM. CXCR4 overexpression was associated with advanced Ann Arbor stages, MYC overexpression, and increased extranodal infiltration; CCR7 was associated with advanced Ann Arbor stages and elevated LDH. Like the case for CCR7, the survival rate of CXCR4-positive DLBCL patients was significantly lower than that of the CXCR4-negative patients. CXCR4CCR7 patients had the lowest survival rate.
There is a positive correlation between CXCR4 overexpression and BM involvement. CXCR4 and CCR7 overexpression is associated with poorer overall survival, especially in CXCR4 and CCR7 copositive patients. CXCR4, CCR7, Ki-67 index, and MYC were independent prognostic factors for DLBCL. Blocking CXCR4 and/or CCR7 can be a novel therapeutic strategy for DLBCL.
已有少数研究评估趋化因子受体 CXCR4 和 CCR7 在弥漫性大 B 细胞淋巴瘤（DLBCL）中的表达；然而，CXCR4 和 CCR7 与骨髓（BM）受累的关系及其对预后的协同作用尚不清楚。本研究对此进行了探讨。
收集 61 例原发性结内 DLBCL 患者和 100 例反应性增生性淋巴结炎患者的标本。采用免疫组化染色检测 CXCR4 和 CCR7 的表达水平；分析这些水平与临床参数的关系以及对总生存的影响。
大多数 DLBCL 患者的恶性淋巴结组织中观察到 CXCR4 和 CCR7 过表达。非生发中心 B 细胞（non-GCB）亚型中 CCR7 表达显著高于生发中心 B 细胞（GCB）亚型；2 种亚型间 CXCR4 阳性率无显著差异。在有 BM 受累的 DLBCL 患者中，CXCR4 在几乎所有 BM 样本中过表达，而 CCR7 在 BM 中低表达。CXCR4 过表达与较晚的 Ann Arbor 分期、MYC 过表达和更多的结外浸润有关；CCR7 与较晚的 Ann Arbor 分期和升高的 LDH 有关。与 CCR7 情况相似，CXCR4 阳性的 DLBCL 患者的生存率明显低于 CXCR4 阴性患者。CXCR4CCR7 患者的生存率最低。
CXCR4 过表达与 BM 受累呈正相关。CXCR4 和 CCR7 过表达与总生存较差相关，特别是在 CXCR4 和 CCR7 共阳性患者中。CXCR4、CCR7、Ki-67 指数和 MYC 是 DLBCL 的独立预后因素。阻断 CXCR4 和/或 CCR7 可能成为治疗 DLBCL 的新策略。
