CXCR4 and CCR7 Expression in Primary Nodal Diffuse Large B-Cell Lymphoma-A Clinical and Immunohistochemical Study

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. CXCR4⁺CCR7⁺ 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.