Lymphangiogenesis in non-Hodgkin's lymphoma and its correlation with cyclooxygenase-2 and vascular endothelial growth factor-C.

We aimed to investigate the correlations between lymphangiogenesis, cyclooxygenase (COX)-2 and vascular endothelial growth factor-C (VEGF-C) in non-Hodgkin's lymphoma (NHL) and their associations with the clinical parameters of patients. A total of 75 patients diagnosed with NHL were enrolled in this study. Of the 75 patients, 14 (18.7%) had low-grade and 61 (81.3%) had aggressive lymphoma. We examined the immunohistochemical expression of COX-2 and VEGF-C and estimated lymphangiogenesis by counting lymphatic vessels expressing lymph vessel endothelial hyaluronan receptor-1 (LYVE-1). Our results showed that lymphatic vessel density (LVD) was positive in 59.0% of the cases with aggressive morphology, while the LVD positive rate of indolent lymphoma was only 28.6% (P=0.039). Both COX-2 and VEGF-C were correlated with lymphangiogenesis (P=0.030 and 0.000, respectively). The expression levels of COX-2 and VEGF-C were significantly correlated (P=0.015). LVD, COX-2 and VEGF-C were not correlated with the gender, age, lactate dehydrogenase (LDH) levels, β2 microglobulin (β2M) levels, extranodal involvement, disease stage, B symptoms or international prognostic index of the patients. In conclusion, lymphangiogenesis was correlated with aggressive histology in NHL. COX-2 and VEGF-C are inducers of lymphangiogenesis and their expression levels were correlated in NHL.