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.