The Interplay Between C-Myc Oncogene Expression and Circulating Vascular Endothelial Growth Factor (sVEGF), Its Antagonist Receptor, Soluble Flt-1 in Diffuse Large B Cell Lymphoma (DLBCL): Relationship to Patient Outcome

• Published in: Leukemia & lymphoma Vol. 45; no. 3; pp. 499 - 506
• Main Authors: Aref, S, Mabed, M, Zalata, K, Sakrana, M, El Askalany, H
• Format: Journal Article
• Language: English
• Published: United States Informa UK Ltd 01.03.2004; Taylor & Francis
• Subjects: Adult; Aged; Angiogenesis; Angiogenesis Inducing Agents; beta 2-Microglobulin - blood; c-Myc; Case-Control Studies; DLBCL; Extracellular Matrix Proteins - blood; Female; Humans; Lymph Nodes - pathology; Lymphoma, B-Cell - diagnosis; Lymphoma, Large B-Cell, Diffuse - diagnosis; Male; Middle Aged; Multivariate Analysis; Outcome; Prognosis; Proto-Oncogene Proteins c-myc - analysis; Proto-Oncogene Proteins c-myc - biosynthesis; Severity of Illness Index; sFlt-1; sVEGF; Treatment Outcome; Vascular Endothelial Growth Factor A - blood; Vascular Endothelial Growth Factor Receptor-1
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/10428190310001607151

The c-Myc is a ubiquitous and multifunctional oncogene. Recently, data obtained from experimental study suggests the involvement of c-Myc oncogene in angiogenesis. In the present study the interrelation of sVEGF, sFlt-1 concentrations and c-Myc oncoprotein expression at diagnosis were assessed in DLBCL and their impact on the patient outcome. Forty-five DLBCL patients beside 10 normal controls were included. C-Myc oncoprotein was assessed by immunohistochemistry. SVEGF and sFlt-1 were determined by enzyme linked immunosorbent assay. C-Myc over-expression was detected in 66.6% of DLBCL. The DLBCL patient group with positive c-Myc over-expression showed significantly higher sVEGF and significantly decreased sFlt-1 as compared to group with negative c-Myc over-expression (P = 0.000 and P = 0.009 respectively). SVEGF was positively correlated to sLDH and s.β2 microglobulin (r = 0.6, P = 0.000, r = 0.69, P = 0.000) respectively. On the other hand sFlt-1 was negatively correlated to sLDH and s.β2 microglobulin (r − 0.25, P > 0.05, r − 0.49, P = 0.001) respectively. The non-living DLBCL group showed significantly higher expression of c-Myc, higher concentration of sVEGF and lower concentration in sFlt-1 level as compared to the living group (P = 0.000 for all). Multivariate analysis revealed that c-Myc over-expression; high sVEGF and normal sFlt-1 levels at diagnosis had independent adverse influence on survival (relative risk: 17.9, 35.7, 29.3, 2.63; P < 0.0001, P < 0.0001, and P = 0.03 respectively) In conclusion: C-Myc over-expression significantly associated with high sVEGF and normal sFlt-1 level in DLBCL patients, suggesting a complex interrelationship between c-Myc oncogene expression and angiogenic regulators. C-Myc over-expression, high sVEGF and normal sFLt-1 levels at diagnosis had an independent adverse influence on survival in DLBCL patients and considered bad prognostic markers.