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

OBJECTIVE: To investigate the colorectal adenomacarcinoma sequence by biparametric 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 biparametric DNA/nuclear protein content flow cytometric analysis in 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 dysplasia and adenocarcinomas, respectively. The difference between normal mucosa and the other groups was statistically significant (P < .05), while no significant differences were detectable between adenomas with different degrees of dysplasia and adenocarcinomas. CONCLUSION: Our results show a decrease in G0-G1A in adenomas with mild/moderate dysplasia, suggesting that modification of the cell cycle may represent an early step in colon carcinogenesis, and they support the hypothesis that disregulation of cell cycle-controlling genes is an early event in the adenoma-carcinoma sequence.