Association between cyclooxygenase-2-expressing macrophages, ulceration and microvessel density in colorectal cancer.
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.
Sheehan
K M
KM
Department of Pathology, Beaumont Hospital, and Royal College of Surgeons in Ireland, Dublin, Ireland. katherinesheehan@hotmail.com
Steele
C
C
Sheahan
K
K
O'Grady
A
A
Leader
M B
MB
Murray
F E
FE
Kay
E W
EW
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
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