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

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.beta2 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.beta2 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.