Colonic aberrant crypts may originate from impaired fissioning: Relevance to increased risk of neoplasia

Don Kristt, Kingsley Bryan, Rivka Gal

Research output: Contribution to journalArticlepeer-review

Abstract

Colonic aberrant crypt loci (ACF) can be identified on the unembedded mucosal surface as clusters of abnormal crypts with enlarged, surface openings. 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 5x 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 he in the formation of enlarged crypt openings. The latter could trap dietary carcinogens as they trap dye, and thereby predispose the CCS to dysplasia.

Original languageEnglish
Pages (from-to)1449-1458
Number of pages10
JournalHuman Pathology
Volume30
Issue number12
DOIs
StatePublished - 1999
Externally publishedYes

Keywords

  • Aberrant crypt foci
  • Cancer
  • Carcinogenesis
  • Colon
  • Colorectal carcinoma
  • Crypt fissioning
  • Crypt replication cycles
  • Dysplasia
  • Hyperplasia
  • Ki-67
  • Risk factors

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