CCL2 Chemokine Gene Expression in Lymph Nodes May Have Prognostic Value in Non-Hodgkin’s Lymphoma.

Background: Non-Hodgkin’s lymphomas (nHL) constitute complex group of lymphoproliferative disorders in which clinical outcome is difficult to predict at the moment of diagnosis. Formation of International Prognostic Index has provided criteria dividing patients into groups of risk, but still new prognostic factors are being searched. There are several reports that some chemokines including CCL2 play a role in progression of solid tumours (bladder, ovarian, non-small cell lung cancer) and increased level of CCL2 has been found in myeloma multiple. CCL2 is the chemokine produced by tumour cells and some stromal cells, such as: fibroblasts, endothelial cells and monocytes. CCL2 is chemoattractant for monocytes, T, NK and dendritic cells and basophlis. CCL2 has also angiogenic activity and is necessary for tumour growth and metastatic process.

Aim: The purpose of this study was to evaluate gene expression of CCL2 chemokine in lymphoma and reactive lymph nodes.

Material and methods: CCL2 gene expression was determined in 37 lymph nodes of lymphoma patients (26 B-cell lymphoma: 12 females and 14 males aged 26–73 years; 4 T-cell lymphoma: males aged 41–81 years; 7 Hodgkin’s lymphoma: 4 females and 3 males aged 21–58 years) and 25 reactive lymph nodes (15 females, 10 males, aged 18–59 years, median age 32 years). Gene expression was determined by the reverse transcription (RT)-polymerase chain reaction method. Scale of expression was 0–3 AU. Statistical analysis was performed using Kruskall-Wallis and Mann-Witney tests (p<0,05).

Results: In lymphoma lymph nodes CCL2 expression was significantly higher (2–3 AU) than in reactive lymph nodes (p=0,0008). Increased CCL2 expression was detected in 19/26 (73%) B-cell lymphoma lymph nodes and all (4/4, 100%) T-cell lymphomas. In reactive lymph nodes 2 AU expression was observed in 7/25 cases (28%). Particularly high expression characterized diffuse large B-cell lymphomas and Burkitt lymphomas. Patients with high CCL2 expression had significantly shorter survival than those with low expression (p=0,004). There was positive correlation between CCL2 expression and Ki-67 proliferation marker (p<0,05; coefficient 0,39).

Conclusions: CCL2 expression is higher in B-cell lymphoma lymph nodes than in reactive lymph nodes. Multivariate analysis has proved CCL2 as independent prognostic factor in nHL.