An apparent exception to the colorectal adenoma-carcinoma carcinogenic pathway is the so-called "de novo" carcinoma that has no evidence of adenoma in its vicinity. Despite the fact that they are often quite small, these lesions appear to bhe more aggressive (i.e. have greater likelihood of lymph node metastases) than carcinomas that clearly arise from surrounding adenomas ("ex-adenoma carcinoma"). The purpose of the present immunohistochemical study was to compare rates of cell adhesion molecule (E-cadherin and beta-catenin) and protease (stromelysin-3 (ST-3)) expression in groups of de novo (n = 64) and ex-adenoma (n = 42) lesions in order to see if their more aggressive behavior is associated with decreased cell adhesion and increased protease expression. Although beta-catenin expression showed abnormalities (decreased or nuclear expression), it did not differ between the two groups. In contrast, the rates of extensive ST-3 expression and decreased E-cadherin expression were significantly higher in de novo group (P = 0.014 and 0.005, respectively). Histopathologically the de novo group had a significantly higher percentage of case with an infiltrative invasion pattern. These differences highlight the more aggressive phenotype of the de novo colorectal cancer and fit with a greater invasive potential of it.

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