SIGNIFICANCE OF APOPTOSIS IN THE PROCESS OF TUMORIGENESIS IN COLORECTAL MUCOSA AND ADENOMAS IN FAP PATIENTS

The relation between proliferation and apoptosis was studied in colore ctal mucosal biopsies (N = 41), tubular adenomas (TA) (N = 104) and tu bulovillous adenomas (TVA) (N = 34) from 37 FAP patients. Proliferativ e activity was determined by cell cycle distribution analysis. In addi tion, transcriptional capacity was determined by chromatin in situ tes ting. For both, DNA flow cytometry was used. Cycling cells were identi fied by immunohistochemical staining with monoclonal antibody Ki67. Th e existence of subdiploid apoptotic cells was derived from DNA and/or DNA/protein patterns. In a follow-up group, the mucosa is characterise d by a balance between proliferation (S % + G2M % = 19) and apoptotic cells (% = 17). The percentage of Ki67 positive cells (16%) correspond s to the percentages mentioned above. In TA, the amount of apoptotic c ells remains unaltered, in TVA it decreases to 8%. At the same time, t he percentage of Ki67 positive cells increases significantly in both T A and TVA (39%, 42%). With patients who underwent surgery due to clini cal signs without histological evidence for malignancy, apoptotic cell s in TA continue to decrease significantly (9%), without any changes i n cycling cells. Only in the carcinoma-bearing bowel, cycling cells in crease to 52%. Here, the percentage of apoptotic cells in TVA reaches the lowest level (5%). A connection between proliferation and apoptosi s was observed in mucosa and TVA. The process of tumorigenesis is char acterised by a stepwise increase in resistance to apoptosis followed b y an increase in cycling cells.