Angiogenesis in nodal B cell lymphomas: a high throughput study.
OBJECTIVE
To assess the biological significance of vascular endothelial growth factor (VEGF) A, VEGF receptor (Flk-1) and cyclooxygenase 2 (COX2) expression with respect to microvessel density (MVD), proliferative activity (Ki-67), expression of p53 and clinical presentation in a large cohort of nodal B cell lymphomas.


METHODS
An immunohistochemical and morphometric study was performed on a validated tissue microarray containing 271 B cell lymphoma specimens, 197 of which included follow-up data. Statistical assessment was done by Pearson's chi(2) test, Spearman's rank correlation coefficient, analysis of variance and survival analysis.


RESULTS
266 (98%) cases were evaluable. Strong VEGF expression was observed in only 20 diffuse large B cell lymphomas (DLBCLs). Flk-1 and COX2 were expressed in 53 and 21 cases, respectively, mainly in DLBCLs, follicular lymphoma (FL) grade 3 and mantle cell lymphomas (MCLs), in a low proportion of cells. MVD decreased in the following order: DLBCLs, FLs, MCLs and small lymphocytic lymphomas/chronic lymphocytic leukaemia (SLL/CLLs). VEGF expression correlated with Ki-67, p53 and COX2 expression in the whole cohort and in DLBCLs. Flk-1 expression correlated with Ki-67 in the cohort and in SLL/CLL and FL grade 1 and 2. COX2 expression correlated with Ki-67 and p53. The analysed angiogenesis parameters did not correlate with clinical parameters or survival.


CONCLUSIONS
Angiogenesis plays a differential role in various B cell lymphomas. Aggressive lymphomas express the potential molecular therapeutic targets VEGF and COX2, and have higher MVD. In a few low proliferation-fraction lymphomas, Flk-1 might have a role in proliferative advantage. Therapeutic strategies aimed at angiogenesis should take into account lymphoma heterogeneity.
Tzankov
Alexandar
A
Institute of Pathology, Medical University of Innsbruck, Innsbruck, Austria. atzankov@uhbs.ch
Heiss
Simone
S
Ebner
Stephanie
S
Sterlacci
William
W
Schaefer
Georg
G
Augustin
Florian
F
Fiegl
Michael
M
Dirnhofer
Stephan
S
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism / Q000473:pathology; D020522:Lymphoma, Mantle-Cell / Q000378:metabolism / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000473:pathology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; D040301:Vascular Endothelial Growth Factor Receptor-2