Expression of N -acetyllactosamine and β1,4-Galactosyltransferase (β4GalT-I) During Adenoma-Carcinoma Sequence in the Human Colorectum

We set out to determine the expression profiles of glycoproteins possessing N-acetyllactosamine, a precursor carbohydrate of sialyl Le(x), during colorectal cancer development. We immunohistochemically analyzed the distribution of N-acetyllactosamine as well as of beta4GalT-I, a member of the beta1, 4-galactosyltransferase family responsible for N-acetyllactosamine biosynthesis, in normal mucosa and in adenoma and carcinoma of the human colorectum. Using monoclonal antibody H11, N-acetyllactosamine was barely detectable in the normal mucosa. In low-grade adenoma, however, N-acetyllactosamine was weakly but definitely expressed on the cell surface, and its expression level was moderately increased in high-grade adenoma and markedly increased in carcinoma in situ as well as in advanced carcinoma. To detect beta4GalT-I, we used a newly developed polyclonal antibody (designated A18G), which is specific for the stem region of human beta4GalT-I. Faint expression of beta4GalT-I was detectable in normal mucosa, and the expression level was moderately increased in low-grade adenoma and in high-grade adenoma and markedly increased in carcinoma in situ and advanced carcinoma. The expression of N-acetyllactosamine was highly correlated with the expression of beta4GalT-I in these tumor cells. These results indicate that the expression level of beta4GalT-I is apparently enhanced during tumorigenesis in the colorectum and that beta4GalT-I mostly directs the carcinoma-associated expression of N-acetyllactosamine on the colorectal tumor cell surface. (J Histochem Cytochem 47:1593-1601, 1999)