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)


CONCLUSIONS
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.
Aref
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Hematology Unit, Clinical Pathology Department, Mansoura Faculty of Medicine, Mansoura, Egypt. Salaharef@yahoo.com
Mabed
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Zalata
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Sakrana
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El Askalany
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D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents; D016022:Case-Control Studies; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000175:diagnosis*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis* / Q000096:biosynthesis; D012720:Severity of Illness Index; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1; D001613:beta 2-Microglobulin / Q000097:blood
D043925:Angiogenesis Inducing Agents; D016326:Extracellular Matrix Proteins; D016271:Proto-Oncogene Proteins c-myc; D042461:Vascular Endothelial Growth Factor A; D001613:beta 2-Microglobulin; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1