Mucinous colon carcinomas with microsatellite instability have a lower microvessel density and lower vascular endothelial growth factor expression.
We determined the association between cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) expression, microvessel density (MVD) and microsatellite instability (MSI) or the histological type in colon adenocarcinomas. Sixty-six cases were studied, 28 MSI+ and 38 MSI-. MSI phenotype was determined using polymerase chain reaction. MVD was assessed after CD31 staining in ten x400 fields (0.96 mm(2)) in the most vascularized areas. VEGF and COX-2 expression were studied by means of immunohistochemistry. MVD positively correlated with the levels of VEGF expression (P=10(-4)) and also with the levels of COX-2 expression (P=0.007). MVD and VEGF expression were lower in MSI+ carcinomas (P=0.002 and P=0.03 respectively). When mucinous tumors were excluded from the statistical analysis, the association between low MVD, low VEGF and MSI status disappeared (P=0.5, P=1, respectively). MSI+ mucinous carcinomas had a lower MVD and VEGF expression than other MSI+ carcinomas (P=0.008 and P=0.004, respectively) and MSI- mucinous carcinomas (P=0.01 and P=0.001, respectively). COX-2 expression was lower in medullary carcinomas (P=0.001). In conclusion, mucinous MSI+ colon carcinomas represent a special group of colon adenocarcinomas relating to angiogenesis, with a lower MVD and VEGF expression than both MSI- mucinous carcinomas and MSI+ non-mucinous carcinomas. A low COX-2 expression could be related to the medullary phenotype. However, this has to be confirmed in a larger series. Finally, the low MVD of MSI+ mucinous colon adenocarcinomas could participate in their overall better prognosis.
Wendum
Dominique
D
Department of Pathology, Hôpital Saint-Antoine, AP-HP, 184 rue du faubourg Saint-Antoine, 75571 Paris Cedex 12, France. dominique.wendum@sat.ap-hop-paris.fr
Boëlle
Pierre-Yves
PY
Rigau
Valérie
V
Sebbagh
Nicole
N
Olschwang
Sylviane
S
Mourra
Najat
N
Parc
Rolland
R
Trugnan
Germain
G
Masliah
Joëlle
J
Fléjou
Jean-François
JF
D002288:Adenocarcinoma, Mucinous / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism; D051546:Cyclooxygenase 2; D004273:DNA, Neoplasm / Q000032:analysis; D016228:Endothelial Growth Factors / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism*; D008565:Membrane Proteins; D008833:Microcirculation / Q000473:pathology; D018895:Microsatellite Repeats / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000473:pathology; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D004273:DNA, Neoplasm; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D008222:Lymphokines; D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases