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Journal of Histochemistry and Cytochemistry, Vol. 47, 1593-1602, December 1999, Copyright © 1999, The Histochemical Society, Inc.

ARTICLE

Expression of N-acetyllactosamine and ß1,4-Galactosyltransferase (ß4GalT-I) During Adenoma–Carcinoma Sequence in the Human Colorectum

Tetsuro Ichikawaa, Jun Nakayamaa, Naoki Sakurab, Tadashi Hashimotob, Minoru Fukudac, Michiko N. Fukudac, and Takao Takid
a Department of Laboratory Medicine, Shinshu University School of Medicine and Central Clinical Laboratories, Shinshu University Hospital, Matsumoto, Japan
b Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan
c Glycobiology Program, Cancer Research Center, the Burnham Institute, La Jolla, California
d Cellular Technology Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan

Correspondence to: Jun Nakayama, Central Clinical Laboratories, Shinshu Univ. Hospital, Asahi 3-1-1, Matsumoto 390-8621, Japan.

We set out to determine the expression profiles of glycoproteins possessing N-acetyllactosamine, a precursor carbohydrate of sialyl Lex, during colorectal cancer development. We immunohistochemically analyzed the distribution of N-acetyllactosamine as well as of ß4GalT-I, a member of the ß1,4-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 ß4GalT-I, we used a newly developed polyclonal antibody (designated A18G), which is specific for the stem region of human ß4GalT-I. Faint expression of ß4GalT-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 ß4GalT-I in these tumor cells. These results indicate that the expression level of ß4GalT-I is apparently enhanced during tumorigenesis in the colorectum and that ß4GalT-I mostly directs the carcinoma-associated expression of N-acetyllactosamine on the colorectal tumor cell surface. (J Histochem Cytochem 47:1593–1601, 1999)

Key Words: tumor-associated, carbohydrate antigen, glycosyltransferase gene family, immunohistochemistry


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