title: Association between cyclooxygenase-2-expressing macrophages, ulceration and microvessel density in colorectal cancer.
abstract: OBJECTIVE
  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. Tauhe aim of this study was to define the relationship between microvessel density (MVD), tumour COX-2 and macrophage COX-2 expression.
  
  
  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.
authors.affiliation: Department of Pathology, Beaumont Hospital, and Royal College of Surgeons in Ireland, Dublin, Ireland. katherinesheehan@hotmail.com
authors.forename: K M
authors.initials: KM
authors.lastname: Sheehan
authors.forename: C
authors.initials: C
authors.lastname: Steele
authors.forename: K
authors.initials: K
authors.lastname: Sheahan
authors.forename: A
authors.initials: A
authors.lastname: O'Grady
authors.forename: M B
authors.initials: MB
authors.lastname: Leader
authors.forename: F E
authors.initials: FE
authors.lastname: Murray
authors.forename: E W
authors.initials: EW
authors.lastname: Kay
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D051546:Cyclooxygenase 2; D004848:Epithelium / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000201:enzymology / Q000473:pathology*; D008565:Membrane Proteins; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D014456:Ulcer / Q000473:pathology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; D051546:Cyclooxygenase 2; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C496540:PTGS2 protein, human