CDX-2 HOMEODOMAIN PROTEIN EXPRESSION IN HUMAN AND RAT COLORECTAL ADENOMA AND CARCINOMA

Cancers share many similarities in growth patterns, cellular morpholog y, and oncofetal antigen expression with embryonic tissue. To better u nderstand the mechanisms underlying malignant transformation and its r elationship to developmental processes, we studied the expression of C dx-2, an intestinal epithelium-specific homeodomain protein, in colore ctal adenoma and carcinoma. By immunohistochemistry with a polyclonal Cdx-2 antibody we have shown that Cdx-2 expression is markedly reduced in the later stages of human colorectal carcinogenesis, namely, high grade dysplasia and invasive carcinoma. The same findings occur in 1,2 -dimethylhydrazine-induced rat colorectal tumors, confirming the paral lels between the rat model and the human disease. As homeodomain prote ins play major roles in directing the regionalization of body parts an d in organogenesis and cellular phenotypic specification, a reduction of Cdx-2 expression in the late stages of colorectal carcinogenesis ma y reflect a concomitant deviation of the neoplastic tissue from the no rmal intestinal epithelial phenotype.