Association between cyclooxygenase-2-expressing macrophages, ulceration and microvessel density in colorectal cancer

Aim : In colorectal carcinomas, cyclooxygenase‐2 (COX‐2) is expressed predominantly by epithelial cells and is implicated in tumour progression. Tumour‐associated macrophages may influence tumour growth, proliferative rate and angiogenesis and also express COX‐2 when activated. Thus they may play an important stromal‐epithelial role in carcinogenesis. Τhe aim of this study was to define the relationship between microvessel density (MVD), tumour COX‐2 and macrophage COX‐2 expression. Methods and results : Sixty‐five cases of formalin‐fixed paraffin‐embedded colorectal cancer were included in the study. Tissues were immunostained for COX‐2, CD68 (macrophage marker) and CD34 (endothelial marker to assess MVD). Thirty‐six cases were grossly ulcerated cancers and 29 cases showed focal/microscopic ulceration. Macrophages were in high concentration at the base of ulcerated areas, and were also diffusely dispersed within tumoral stroma. However, the pattern of macrophage COX‐2 expression revealed two populations of macrophages—those deep within the tumour (negative for COX‐2) and those at the base of ulcers (positive for COX‐2). In all cases, the tumour epithelial cells expressed COX‐2. MVD was higher at the base of ulcers, adjacent to COX‐2+ macrophages, and was lower deep within the tumour. Conclusions : In colorectal cancers, macrophages may have a dual role. Those concentrated at the base of the ulcers, where there is an associated high MVD, may induce angiogenesis, but their function may be in a healing/repair process. The lack of COX‐2+ macrophages and lower MVD deep within the tumour suggests that it may be the epithelial COX‐2 component that is important in tumour progression.