Proliferating Endothelial Cells and Leukocyte Infiltration as Prognostic Markers in Colorectal Cancer

Background & Aims Leukocyte infiltration in tumors is dependent on angiogenic potential. In this study we aimed to retrospectively investigate the angiogenic potential in archival colorectal cancer (CRC) tissues and its relationship to amount and composition of the inflammatory infiltrate. Methods In tumor tissues of 117 CRC patients with a 12-year follow-up, microvessel density (MVD) and proliferating endothelial cells (ECs) were assessed by CD31/CD34 double staining with the proliferation marker Ki-67. Leukocyte infiltration was determined by using CD45, CD3, CD8, CD16, CD20, and CD68 antibodies in peritumoral, tumor stroma, and intratumoral areas. Results Proliferating ECs, but not MVD, are correlated to Dukes' stage and survival in CRC (P < .05). This parameter correlated significantly with the expression of vascular endothelial growth factor (r = 0.82; P < .012). The number of inflammatory cells in the tumor stroma and cells infiltrated into the tumor cell nests, but not of peritumoral leukocytes, predicted patient survival. This was most obvious for T lymphocytes (CD3; P < .05) and polymorphonuclear cells (CD16; P < .04). We found a significant relationship between angiogenesis parameters and infiltrated leukocytes (r = −0.70; P < .02). Combination of high numbers of infiltrated leukocytes and low amounts of proliferating ECs demonstrated to be an improved prognostic value compared with either parameter alone (P < .006). Conclusions We found a correlation between the intrinsic tumor parameters of ongoing angiogenesis and leukocyte infiltration with prognosis and survival in CRC. These findings have a potential impact on therapeutic applications for both antiangiogenesis as well as immunotherapy.