PROTEIN MARKERS FOR MALIGNANT TRANSFORMATION OF THE COLON

Accurate assessment of risk of developing colorectal carcinoma among p atients with chronic ulcerative colitis and familial adenomatous polyp osis has been difficult. We have previously proposed that certain pre- malignant conditions of the colon result in amplification of one or mo re oncogenes and overexpression of their protein products, which may p rovide a predictive index of the likelihood of subsequent malignant tr ansformation. In this paper we have evaluated tissue processing and me thods of determining several proteins known to be prognostic factors i n breast carcinoma: cathepsin D (CD), epidermal growth factor receptor s (EGF receptors), and the protein product of the related oncogene, HE R-2/neu (c-erb B-2). Expression of CD and HER-2/neu protein was measur ed by monoclonal antibody-based EIA and ELISA. EGF receptors were meas ured by radioligand binding with [I-125]EGF using biopsies of ''normal '' non-neoplastic colon, chronic ulcerative colitis, Crohn's colitis, familial adenomatous polyposis and colon carcinoma. Normal colonic muc osa (18 patients) contained all prognostic markers examined. CD levels were elevated in many specimens of colonic diseases, including colon carcinoma. HER-2/neu and EGF receptors had median values similar in al l samples regardless of diagnosis. Reference ranges and distribution p rofiles for each factor were determined in normal and neoplastic colon . In addition, the expression in situ of each factor was measured usin g serial biopsies of colon from the following sites:ascending, transve rse, descending, sigmoid and rectum. These data are being used to eval uate the expression of CD, EGF receptors, and HER-2/neu protein as pre dictive markers of increased risk for colon carcinoma.