DNA/nuclear protein content in the evaluation of cell cycle modifications during colon carcinogenesis

OBJECTIVE: To investigate the colorectal adenoma-carcinoma sequence by bipa rametric DNA/nuclear protein flow cytometry with the aim of evaluating cell cycle modifications during carcinogenesis. STUDY DESIGN: Paraffin-embedded specimens of 27 adenomas with mild/moderate dysplasia, 20 adenomas with severe dysplasia/intramucosal adenocarcinomas, 28 adenocarcinomas and 14 normal colon mucosa specimens were analyzed by b iparametric DNA/nuclear protein content flow cytometric analysis ill order to evaluate cell cycle modifications during colorectal carcinogenesis. RESULTS: The mean G0-G1A fraction of the cell cycle was 50.6% (SD +/- 17.2) , 25.7% (SD +/- 15.1), 27.8% (SD +/- 11.7) and 29% (SD +/- 13.8) for normal mucosa, adenomas with mild/moderate dysplasia, adenomas with severe dyspla sia and adenocarcinomas, respectively. The difference between normal mucosa and the other groups mas statistically significant (P < .05), while no sig nificant differences were detectable between adenomas with different degree s of dysplasia and adenocarcinomas. CONCLUSION: Our results show a decrease in G0-G1A in adenomas with mild/mod erate dysplasia, suggesting that modification of the cell cycle may represe nt an early step in colon carcinogenesis, and they support the hypothesis t hat disregulation of cell cycle-controlling genes is an early event in the adenoma-carcinoma sequence.