INTEGRIN BETA-4 EXPRESSION IN COLORECTAL-CANCER

Integrin alpha 6 beta 4 plays an important role in the interaction of epithelia with basement membranes, and its expression appears to be pr ofoundly altered during tumor progression. Using a quantitative immuno chemical assay, we investigated the expression of the beta 4 subunit a ssociated with alpha 6 in 25 primary carcinomas, and in matching norma l mucosae. alpha 6 beta 4 was expressed in all the carcinoma and mucos a samples. The highest beta 4 levels were detected in tumors at high c linical stage (Dukes' stage C). Furthermore, beta 4 reactivity inverse ly correlated with the degree of differentiation. By immunohistochemis try,beta 4 expression was particularly strong in the epithelium lining the upper third of the crypts and the absorbing surface of normal muc osa. In villous adenomas, beta 4 immunostaining tended to be enhanced in the epithelium lining the outer surfaces of neoplastic villi, but o nly 5 of 8 samples tested scored positive. In carcinomas, beta 4 expre ssion was detected in 18 of 21 samples tested, and was strongly influe nced by the pattern of tumor growth and by the type and level of diffe rentiation. Carcinomas, or areas of carcinomas, with cohesive and diff erentiated growth pattern demonstrated weak beta 4 expression at the t umor-stroma interface. Carcinoma cells at the lumenal surface of the i ntestine, and carcinomas, or areas of carcinomas, composed of small cl usters of cells surrounded by stroma, demonstrated strong beta 4 expre ssion. Altogether, our observations indicate that in colorectal tumors the expression of the beta 4 subunit is strongly influenced by microe nvironmental factors and tends to increase in high stage, poorly diffe rentiated lesions.