title: Colonic aberrant crypts may originate from impaired fissioning: relevance to increased risk of neoplasia.
abstract: Colonic aberrant crypt foci (ACF) can be identified on the unembedded mucosal surface as clusters of abnormal crypts with enlarged, surface opening. Because dysplasia is frequent, and may be a precursor of carcinoma, epithelial changes have been well studied. However, the basis for the distinctive changes in crypt architecture remain unclear. We hypothesized that some of the architectural alterations of aberrant crypts may reflect impaired fissioning during normal crypt duplication cycles. Fissioning begins at the crypt base. Using morphometric and immunocytochemical approaches, we examined 55 human ACF, both dysplastic and nondysplastic, for their architectural features. Non-ACF mucosa was compared. Microscopically, all lesions contained crypts that were attached, paired, dilated, and angulated. In 3 dimensions, these features related to multiple, individual complexes of connected crypts, referred to as connected crypt structures (CCSs). CCSs terminated in enlarged surface openings (2 to 5 x normal) which are morphometrically equivalent to the macroscopic aberrant crypts (P > .1). These openings trap marker dye. Support for an origin of CCSs in impaired basal fissioning is 3-fold. Crypt profiles in ACF are twice as frequent in basal mucosa as superficially (P < .001); in normal mucosa, the ratio is 1. In a CCS with vertically connected, co-planar crypts, the upper parent crypt diameter was the sum of diameters of inferiorly attached daughter crypts (P > .1). Proliferating cell marker, Ki-67, is not expressed at attachment points. In non-ACF mucosa, isolated CCSs consistently occur at foci of mechanical crypt distortion such as mucosal folds. We conclude that a CCS is a fundamental component of ACF of all histotypes. Impairment of normal crypt fissioning is probably a major factor in the histogenesis of CCSs, which often occurs in settings of mechanical distortion of the mucosa. The pathological significance of this process may be in the formation of enlarged crypt openings. The latter could trap dietary carcinogens as they trap dye, and thereby predispose the CCS to dysplasia.
authors.affiliation: Department of Pathology, Rabin Medical Center (Golda Campus), HaSharon Hospital, Petach Tikvah, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Kristt
authors.forename: K
authors.initials: K
authors.lastname: Bryan
authors.forename: R
authors.initials: R
authors.lastname: Gal
mesh_terms: D002455:Cell Division; D003106:Colon / Q000473:pathology*; D003110:Colonic Neoplasms / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology*; D019394:Ki-67 Antigen / Q000032:analysis; D012307:Risk Factors
chemical_list: D019394:Ki-67 Antigen