Angiogenesis in nodal B cell lymphomas: a high throughput study

• Published in: Journal of clinical pathology 2007-05, Vol.60 (5), p.476-482
• Main Authors: Tzankov, Alexandar, Heiss, Simone, Ebner, Stephanie, Sterlacci, William, Schaefer, Georg, Augustin, Florian, Fiegl, Michael, Dirnhofer, Stephan
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; Biomarkers, Tumor - metabolism; Cell Proliferation; COX2; cyclooxygenase 2; Cyclooxygenase 2 - metabolism; diffuse large B cell lymphoma; DLBCL; Female; FL G1&2; FL grade 1 and 2; follicular lymphoma; Genes; Hematologic and hematopoietic diseases; Humans; Immunoenzyme Techniques; Investigative techniques, diagnostic techniques (general aspects); Kinases; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma; Lymphoma, B-Cell - metabolism; Lymphoma, B-Cell - pathology; Lymphoma, Large B-Cell, Diffuse - metabolism; Lymphoma, Large B-Cell, Diffuse - pathology; Lymphoma, Mantle-Cell - metabolism; Lymphoma, Mantle-Cell - pathology; Male; mantle cell lymphoma; MCL; Medical sciences; Microcirculation - pathology; microvessel density; Middle Aged; MVD; Neoplasm Proteins - metabolism; Neovascularization, Pathologic - metabolism; Original; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Rodents; SLL/CLL; small lymphocytic lymphoma/chronic lymphocytic leukaemia; Survival Analysis; tissue microarray; TMA; Tumor Suppressor Protein p53 - metabolism; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor Receptor-2 - metabolism; VEGF
• ISSN: 0021-9746; 1472-4146
• DOI: 10.1136/jcp.2006.038661

Aim: 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 χ2 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.