Do any microcirculation changes reflect the malignant transformation in the intestinal tract during the multistep carcinogenesis?

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Apc^(Min/+) mice provide a unique orthotopic model for the development of spontaneous adenomatous polyposis and subsequent carcinomas, termed the adenoma-carcinoma sequence. In the current study, we sought to clarify the relationship between the patterns of tumor angiogenesis and the sequence of neoplastic transformation in intestinal epithelia, by the morphological characterization of this tumor models. We found that structural abnormalities of tumor vessels and the pattern of tumor angiogenesis in benign tumors resembled that in malignant tumors. Several angiogenic markers, such as VEGF were overexpressed in pre-neoplastic intestinal lesions from very early stages during the adenoma-carcinoma sequence in both mice and humans. A novel intrinsic angiogenic factor, Vasohibin-2 protein was detected around tumor blood vessels in adenocarcinomas in situ, but was absent from adenomas during early stages of Apc^(Min/+) tumors. These results indicated that malignant changes in local vascular networks occurred earlier than malignant transformation of the intestinal epithelia. Therefore, we suggest that microvascular changes in preneoplastic adenomatous polyposis may be an important diagnostic sign for the progression of intestinal adenocarcinoma and may be useful to predict the transformation of tumors from a benign to a malignant state