COLONIC ABERRANT CRYPT FOCI ARE ASSOCIATED WITH INCREASED EXPRESSION OF C-FOS - THE POSSIBLE ROLE OF MODIFIED C-FOS EXPRESSION IN PRENEOPLASTIC LESIONS IN COLON CANCER

Aberrant crypt foci represent the earliest detectable lesions of colon cancer. The expression of c-fos in these aberrant crypts was determined by in situ hybridization and immunohistochemistry. These lesions were induced in the colonic epithelium with azoxymethane using the rat model system. Expression of c-fos was markedly increased in the aberrant colonic crypts. Increases of approximately 60 and approximately 70% in the proportion of epithelial cells labelled were observed in the early and advanced aberrant crypts respectively. This was found to be statistically significant (P < 0.001). Consistent with cell proliferation patterns in the colonic crypts, the epithelial cells of the lower crypt had greater levels of c-fos mRNA than those of the upper part of the crypts. In addition, immunohistochemical staining with c-fos polyclonal antibodies demonstrated increased levels of c-fos protein in aberrant crypts. This combined approach using in situ hybridization and immunohistochemistry has shown that increased c-fos expression at the RNA level in these lesions is associated with increased amounts of c-fos protein. Since c-fos has been implicated in the process of cell proliferation and differentiation, modifications in its expression may be significant to understanding the mechanisms whereby preneoplastic lesions transform to neoplastic lesions in colon cancer.