HISTOMORPHOLOGICAL AND IMMUNOHISTOCHEMICAL CHARACTERIZATION OF COLONIC ABERRANT CRYPT FOCI IN RATS - RELATIONSHIP TO GROWTH-FACTOR EXPRESSION

Many studies have been conducted to assess the potential preneoplastic nature of colonic aberrant crypt foci (ACF), but still the biological significance of these foci and their relationship to colon neoplasia remains to be elucidated, In the present paper a battery of variables suggested to be indicative for colon cancer development has been studi ed in relation to ACF in rats, These include: (i) the degree of dyspla sia; (ii) the type of mucus production; (iii) the cellular immunohisto chemical expression and distribution of transforming growth factors al pha and beta and their respective receptors, epidermal growth factor r eceptor and transforming growth factor beta receptors I and II and pho sphorylated cellular tyrosine, The parameters have been investigated i n ACF selected from a previous study where the foci were induced under different circumstances, leading to disparities in the number as well as the crypt multiplicity obtained, The present study showed that for all parameters investigated, apart from sialomucin production, the di fferent experimental conditions had no effect on the individual ACF, i rrespective of the number and distribution of the different categories of ACF among the various diets, However, it was shown that the degree of dysplasia correlated strongly with crypt multiplicity and that all the investigated ACF lacked expression of transforming growth factor alpha and expressed a reduced amount of transforming growth factor bet a compared with normal crypts, These observations may indicate that AC F are preneoplastic lesions and supports the suggestion that they may, at least in the rat, have the potential to gradually progress to tumo rs, but no single ACF showed particular characteristics indicating spe cific proneness to tumor development, The study could not confirm the presence of sialomucin-producing ACF as a valid marker for tumor devel opment.