Vascular endothelial growth factor (VEGF)-C and its receptor tyrosine kinase VEGFR-3 are critical regulators of lymphangiogenesis. Their expression has been observed in a variety of solid tumors and was associated with lymph node metastasis in patients. The aim of this study was to evaluate whether aggressive lymphatic malignant cells express VEGF-C and its receptor VEGFR-3 and whether the expression correlates with intratumoral microvessel density, and patient outcome. Pathological specimens were taken at diagnosis from 29 diffuse large B-cell lymphoma (DLBCL) patients (11 men, 18 females, mean age 70 years) who were diagnosed between the years 1997–2001. The specimens were evaluated by immunohistochemical staining to determine the expression of VEGF-C and VEGFR-3 and the microvessel count (by factor-VIII-related antigen). All lymphoma specimens demonstrated positive staining for VEGF-C and VEGFR-3 with high intensity staining in 50% and 68% of the specimens respectively. The mean microvessel count was 58 (range 23–120) and blood vessels in all specimens demonstrating positive staining for both VEGF-C and VEGFR-3 (strong in 25% and 58% respectively). We found a significant correlation between high serum levels of β2 microglobulin and high VEGFR-3 staining. High intensity staining was found in 77% of the patients with high β2 microglobulin compared to 44% of the patients with normal β2 microglobulin level (p=0.03).

The patients who expressed high intensity VEGFR-3 staining had worse survival. In the 13 patients who lived more than 5 years, only 46% of them demonstrated high intensity staining while 85% of patients that lived less than 5 years demonstrated such staining (p=0.01). The median event free survival (EFS) was 21 months. A significantly higher proportion of the patients with low EFS (lower than 21 months) demonstrated high intensity staining for VEGFR-3, (p=0.01)

These results suggest that DLBCL tumors express both VEGF-C and its receptor (VEGFR-3) and that this signaling pathway may be associated with patient’s prognosis.

Figure
View largeDownload slide

Figure

Topics:
diffuse large b-cell lymphoma, vascular endothelial growth factor c, vascular endothelial growth factor receptors, vascular endothelial growth factor a, antigens, lymph node metastasis, lymphoma, neoplasms, receptor protein-tyrosine kinases, solid tumors

Author notes

Corresponding author

2005, The American Society of Hematology
2005
Sign in via your Institution