Wendum Dominique, Boëlle Pierre-Yves, Rigau Valérie, Sebbagh Nicole, Olschwang Sylviane, Mourra Najat, Parc Rolland, Trugnan Germain, Masliah Joëlle, Fléjou Jean-François
Department of Pathology, Hôpital Saint-Antoine, AP-HP, 184 rue du faubourg Saint-Antoine, 75571 Paris Cedex 12, France.
Virchows Arch. 2003 Feb;442(2):111-7. doi: 10.1007/s00428-002-0737-3. Epub 2002 Dec 7.
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.
我们确定了环氧化酶-2（COX-2）、血管内皮生长因子（VEGF）表达、微血管密度（MVD）与结肠腺癌微卫星不稳定性（MSI）或组织学类型之间的关联。共研究了66例病例，其中28例为MSI+，38例为MSI-。使用聚合酶链反应确定MSI表型。在十个x400视野（0.96平方毫米）中最血管化的区域进行CD31染色后评估MVD。通过免疫组织化学研究VEGF和COX-2表达。MVD与VEGF表达水平呈正相关（P = 10^-4），也与COX-2表达水平呈正相关（P = 0.007）。MSI+癌中的MVD和VEGF表达较低（分别为P = 0.002和P = 0.03）。当在统计分析中排除黏液性肿瘤时，低MVD、低VEGF与MSI状态之间的关联消失（分别为P = 0.5和P = 1）。MSI+黏液腺癌的MVD和VEGF表达低于其他MSI+癌（分别为P = 0.008和P = 0.004）以及MSI-黏液腺癌（分别为P = 0.01和P = 0.001）。髓样癌中的COX-2表达较低（P = 0.001）。总之，黏液性MSI+结肠腺癌代表了一组与血管生成相关的特殊结肠腺癌，其MVD和VEGF表达低于MSI-黏液腺癌和MSI+非黏液腺癌。低COX-2表达可能与髓样表型有关。然而，这必须在更大的系列研究中得到证实。最后，MSI+黏液性结肠腺癌的低MVD可能参与其总体较好的预后。
