Serrated
adenoma of the colorectum is a recently proposed entity characterized by a saw-toothed structure of hyperplastic
polyp and cytologic atypia of tubular
adenoma. To clarify the role of apoptosis in morphogenesis of serrated
adenoma, we investigated apoptotic indices and expression of apoptosis-related
antigens in the
tumor cells. Thirty-eight serrated
adenomas were examined by the nick-end
DNA labeling method and immunostained for CD95 (Fas), bcl-2, bax, and p53. Thirty-seven hyperplastic
polyps, 48 tubular
adenomas, and 16 sections containing normal colonic mucosa were similarly examined for comparison. The apoptotic indices in the upper and middle zones of the crypts of serrated
adenomas and hyperplastic
polyps were lower than those of normal colon mucosa and tubular
adenomas with statistically significant differences. The CD95 expression was diffusely observed throughout the epithelium of normal crypts and tubular
adenomas, whereas it was reduced in serrated
adenomas and hyperplastic
polyps. The bcl-2 expression was confined to the basal crypts in the latter two lesions but was diffuse throughout the neoplastic epithelium in tubular
adenomas. The bax expression was increased in serrated
adenomas and tubular
adenomas but was decreased in hyperplastic
polyps. Overexpression of p53
protein was observed in 50% of serrated
adenomas, none of hyperplastic
polyps, and 14% of tubular
adenomas. These findings suggest that inhibition of apoptosis is caused by reduced CD95 expression in serrated
adenomas and hyperplastic
polyps, which may induce the characteristic saw-toothed structure in these lesions. Based on the similarities and differences between serrated
adenoma and hyperplastic
polyp observed in the present study, a progression from the latter to the former lesion may be postulated.