Integrin β4 expression in colorectal cancer

Integrin α6β4 plays an important role in the interaction of epithelia with basement membranes, and its expression appears to be profoundly altered during tumor progression. Using a quantitative immunochemical assay, we investigated the expression of the β4 subunit associated with α6 in 25 primary carcinomas, and in matching normal mucosae. α6β4 was expressed in all the carcinoma and mucosa samples. The highest β4 levels were detected in tumors at high clinical stage (Dukes' stage C). Furthermore, β4 reactivity inversely correlated with the degree of differentiation. By immunohistochemistry, β4 expression was particularly strong in the epithelium lining the upper third of the crypts and the absorbing surface of normal mucosa. In villous adenomas, β4 immunostaining tended to be enhanced in the epithelium lining the outer surfaces of neoplastic villi, but only 5 of 8 samples tested scored positive. In carcinomas, β4 expression was detected in 18 of 21 samples tested, and was strongly influenced by the pattern of tumor growth and by the type and level of differentiation. Carcinomas, or areas of carcinomas, with cohesive and differentiated growth pattern demonstrated weak β4 expression at the tumor-stroma interface. Carcinoma cells at the lumenal surface of the intestine, and carcinomas, or areas of carcinomas, composed of small clusters of cells surrounded by stroma, demonstrated strong β4 expression. Altogether, our observations indicate that in colorectal tumors the expression of the β4 subunit is strongly influenced by microenvironmental factors and tends to increase in high stage, poorly differentiated lesions.