Sessile serrated
adenomas and traditional serrated
adenomas are pathogenetically related to inhibition of apoptosis.
Survivin and
hedgehog proteins, including sonic hedgehog, patched, and smoothened, inhibit apoptosis, with
hedgehog proteins forming a signal transduction cascade implicated in digestive
cancers. This study compares
survivin and
hedgehog protein expression in serrated
polyps and tubulovillous
adenomas. Biopsies of sessile serrated
adenomas (48) and traditional serrated
adenomas (10) diagnosed during 2005 were retrieved from our files. Biopsies of normal mucosa (10), hyperplastic
polyps (14), and tubulovillous
adenomas (22) were used for comparison. Immunohistochemistry for
survivin, sonic hedgehog, patched, and smoothened was graded as high or low grade. chi(2) tests were used to evaluate correlation between
polyp type and
survivin and hedgehog expression. Traditional serrated
adenomas were also compared to sessile serrated
adenomas with foci of cytological dysplasia (11 cases) with respect to MLH1 and p53 expression. Sessile serrated
adenomas showed high-grade nuclear and cytoplasmic expression of
survivin at the bottom of crypts more frequently than tubulovillous
adenomas (60% versus 18%, P = .001 [nuclear]; 54% versus 18%, P = .005 [cytoplasm]), the latter showing a top-heavy pattern of staining.
Survivin expression in hyperplastic
polyps was similar to sessile serrated
adenomas, being bottom-heavy, whereas traditional serrated
adenomas showed diffuse staining throughout crypts. Although traditional serrated
adenomas showed high-grade expression of sonic hedgehog more frequently than tubulovillous
adenomas (90% versus 18%; P < .001), sonic hedgehog, patched, and smoothened expression was low grade among normal mucosa, hyperplastic
polyps, and sessile serrated
adenomas. All cytological dysplasias showed increased p53 expression within dysplastic foci, and MLH1 was also lost within dysplastic foci in 4 cases; traditional serrated
adenomas showed intact MLH1 expression and minimal p53 expression throughout.
Survivin expression is localized to the bottom of crypts in sessile serrated
adenomas and hyperplastic
polyps, whereas tubulovillous
adenomas show top-heavy expression. Traditional serrated
adenomas express
survivin throughout crypts, suggesting intersection between the serrated and conventional
adenoma-
cancer pathways. Sonic hedgehog up-regulation is characteristic of traditional serrated
adenomas, distinguishing this entity from other colorectal
polyps.