Colorectal proliferation and apoptosis in serrated versus conventional adenoma-carcinoma pathway:: Growth, progression and survival

Background: Hyperplastic polyp, serrated adenoma and serrated adenocarcinoma form a morphological continuum, and are likely to be biologically related. The growth rate and malignant conversion rate of serrated adenoma are postulated to be higher than those of conventional adenoma. Methods: Immunohistochemistry for M30 and Ki67 was used to compare apoptosis and proliferation in colorectal hyperplastic polyps, serrated adenomas and serrated adenocarcinomas, and in relation to conventional adenomas and adenocarcinomas. Results: There was an abrupt increase in the apoptosis in carcinomas of serrated adenoma - serrated adenocarcinoma pathway, indicating that inhibition of apoptosis is not maintained in serrated adenocarcinomas. Proliferation was significantly lower at the invasive margin than in the central part in adenocarcinomas, particularly in serrated adenocarcinomas ( P < 0.005, Wilcoxon). Apoptosis was lower at the invasive margin than in the central part in serrated adenocarcinomas, but not in conventional adenocarcinomas. Conclusions: Disordered regulation of apoptosis occurs later in serrated pathway than in conventional adenoma-carcinoma pathway during malignant conversion. Serrated adenoma growth is not likely to be slower than adenoma growth, as judged by the proliferation and apoptosis rates in serrated adenomas and adenomas. In cancer, the decrease of proliferation and apoptosis in the invasive margin is likely to influence the behaviour of the tumour.