The overall goal of this proposal is to evaluate the prevalence and prognostic value of """"""""cancer associated"""""""" markers in normal, premalignant and malignant human colorectal tissue. Importantly, the ability of these markers to predict the development of metachronous lesions in patients with resected colorectal cancer and premalignant adenomatous polyps will be analyzed. In a prospective study, biopsies of normal rectum, sigmoid and ascending colon will be obtained during colonoscopy. Regional differences in mucus glycoproteins (lectin binding), calcium activated proteins and cellular proliferation (ornithine decarboxylase activity and polyamine levels) will be determined and compared among and between patients with and without adenomatous polyps. Analysis of regional differences in these parameters may help explain the predilection of tumors to occur in the distal colon and rectum. Similar observation will be made on resected adenomatous polyps and colorectal cancer. Patients with resected polyps or cancer will then undergo surveillance colonoscopy to document metachronous neoplastic lesions. The parameters used to assess cellular growth and differentiation will be correlated with recurrence of neoplastic disease and survival. In a retrospective study, lectin binding and flow cytometric analysis of paraffin embedded adenomatous polyps will be determined in patients who have undergone surveillance colonoscopy. The direct clinical benefit of this study is to determine the need and timing of surveillance colonoscopy in patients with a history of colonic adenomatous polyps and cancer. The more fundamental benefit will be to elucidate potential biochemical changes that hallmark transformation of normal to premalignant to malignant colorectal tissue. Parallel observations of changes in calcium binding proteins, mucus glycoproteins and cellular proliferation will be made in dimethylhydrazine-induced colon carcinoma in the rat. Regional and sequential changes will be measured during carcinogenesis. The proposed studies will provide direct comparisons of changes that occur in human colon neoplasia and animal models of carcinogenesis.
