Angiogenesis in immunophenotypic subtypes of diffuse large B cell lymphoma

Diffuse large B cell lymphoma (DLBCL) is both common and aggressive, with less than 50% overall survival, but the heterogeneity in clinical behavior has not been amenable to histologic analysis. Gene expression profiling has uncovered biologically and prognostically distinct subgroups of DLBCL. The germinal center (GC)‐like subtype immunostains positive for bcl6, CD10 and HGAL and shows better overall survival than the activated peripheral blood B cell (ABC)‐like subtype, which immunostains positive for MUM1. Angiogenesis, and the proangiogenic growth factor VEGF, have a known role in solid neoplasia and evidence is mounting for a role in hematolymphoid neoplasia as well. We set out to assess the role of angiogenesis and local tumor VEGF expression in the context of clinically and biologically relevant subtypes of DLBCL. We have used immunohistochemistry to assess tissue microarrays of DLBCLs for markers of GC versus ABC immunophenotype (bcl6, CD10, HGAL and MUM1), VEGF, and microvessel density assessed by CD34 immunostaining. Non‐supervised hierarchical clustering reproduced the known GC‐like and ABC‐like subgroups of DLBCL. VEGF expression and microvessel density clustered most closely with each other, and also with HGAL, bcl6 and CD10, markers of GC‐like subtype. Given that GC‐like subtype is associated with better overall survival, it is possible that locally retained VEGF and consequent locally increased angiogenesis and vascular permeability could contribute to survival, perhaps through increased delivery of chemotherapeutic agents to tumor. Funding source: grant NIH P01CA 34233.