Characterization of Neoangiogenesis and EphrinB2 Expression in Association with CD163+ Macrophages at the Tumor-Host Interface in FL and DLBCL
Mina Jamali, Elizabeth Hyjek, Kenneth Cohen, James W Vardiman. University of Chicago, Chicago, IL
Background: EphB4 receptor tyrosine kinase and its cognate ligand EphrinB2 regulate induction/maturation of neovessels. Their role has been explored in vitro, in mice and many human cancers, with inhibition of interaction shown to arrest neoangiogenesis, vessel maturation and pericyte recruitment. Recent research in a mouse model suggests EphB4/EphrinB2 may interact with tumor-associated macrophages (TAMs) in the microenvironment, especially at the invasive tumor front, with potential novel therapeutic implications from blockade of this interaction. Few studies have addressed the role of angiogenesis in human lymphomas and, to date, none have sought to implicate the Eph family. Here, we investigate microvessel density (MVD), EphrinB2-expressing blood vessels and TAMs in human follicular lymphomas (FLs) and diffuse large B-cell lymphomas (DLBCLs) at the tumor-fat interface of lymph node (LN) biopsies.
Design: We evaluated 12 and 11 cases of FL and DLBCL, respectively, from formalin-fixed paraffin-embedded excisional LN biopsies from the University of Chicago archives (2000-2011).Eleven cases of follicular hyperplasia or quiescent LNs were used as controls (Cs). Slides were digitally scanned and examined both semi-quantitatively and by digital image analysis.Vascular and microenvironmental cells expressing CD34,EphrinB2 and CD163 localized to the tumor-fat interface in 3 fields at 400x were quantified and compared between the study groups.
Results: Collectively, the means of the CD34+ MVD were comparable between DLBCL and C groups but showed a significantly higher trend of interface neovascular angiogenic sprouts in FLs. Interface recruited CD163+ cell numbers were significantly higher in DLBCLs than in both FLs and Cs (p<0.0001). EphrinB2-expressing blood vessel sprouts was significantly increased in FLs but not in DLBCL as compared to Cs. Results were reproducible by digital and semi-quantitative analyses. We found a correlation between CD34+ and EphrinB2+ vessels (Spearman r=0.9, P=0.004) and EphrinB2+ and CD163+ expression (r=0.6, P=0.5) in FLs (for digital analysis only).
Conclusions: Increased EPhrinB2+ CD34+ neovessels in concert with CD163+ TAMs at the tumor-fat interface is seen in FLs but not DLBCLs. This represents the first exploration of possible interplays between these vascular/stromal elements in creating pre-neoplastic niches that may contribute to lymphomagenesis and novel targets for therapy.
Monday, March 19, 2012 1:00 PM
Poster Session II # 213, Monday Afternoon