Acetylcholinesterase in Hirschsprung?s disease

Abstract

The association between the congenital absence of colonic ganglion cells and an increased acetylcholinesterase (AChE) expression in the affected tissue is of diagnostic importance in Hirschsprung's disease (HSCR). Investigation of AChE's function in development may also help unravel some of the complex pathophysiology in HSCR. Normal nerves do not stain for AChE, but increased AChE expression is associated with the hypertrophied extrinsic nerve fibres of the aganglionic segment in HSCR. Although a high degree of histochemical diagnostic accuracy exists, results are not always uniform, and false positives and false negatives are reported. False negative results are primarily related to age, and an absence of AChE reaction does not exclude HSCR in neonates within the first 3 weeks after birth. AChE staining results may lack uniformity, resulting in a number of technical modifications that have been made to improve standardization of AChE staining. At least two distinct histological patterns are described, types A and B. The interpretation of increased AChE staining patterns in ganglionated bowel at the time of surgical pull-through remains a problem in patients with HSCR. The development of rapid staining techniques has helped to identify normal ganglionated bowel with greater certainty. The presence of fine AChE neurofibrils in the ganglionated segment has contributed to the debate surrounding intestinal neuronal dysplasia. Quantitative assay of cholinesterase activity confirms the pattern of histochemical staining. AChE is particularly increased in relation to butrylcholinesterase, with one molecular form, the G4 tetrameric form, predominating. It is likely that the raised levels of AChE in aganglionic tissue are the transcriptional consequence of the abnormalities in signalling molecules that characterize HSCR. Evidence suggests that this AChE is functioning in a nonenzymatic capacity to promote cell adhesion and differentiation and that the hypertrophied nerves and neurofibrils may be the result of this increased AChE expression.

Cholinesterases are down-expressed in human colorectal carcinoma

“…The prevalence of the GPI-anchored AChE species over the other variants agrees with the higher content of AChE-H than AChE-T mRNAs in colorectal pieces. Albeit fluorescence 'in situ' hybridization (FISH) assays are needed for ascribing AChE mRNAs to particular intestinal cells, the observation of asymmetric AChE in smooth muscle [26], besides its absence from epithelial cells scraped from intestine [24] and from Caco-2 cells [27] support the muscular origin of the A 12 AChE species identified in gut ( [28], and this work). Moreover, the great increase of G 4 A AChE in Hirschsprung's disease, which arises from hypertrophy of submucosal nerve trunks [28] points to the neuronal origin of intestinal G 4 A AChE.…”

Behind an enteric neuron there may lie a glial cell

“…Mutations in the Parkin gene on chromosome 6 cause autosomal recessive, juvenile-onset parkinsonism (AR-JP), the most common form of early-onset disease (3,4). The Parkin gene encodes a 465 amino acid protein consisting of a ubiquitin-like domain and a RING-box domain containing two RING finger motifs separated by an in-between-RING finger motif (Figure 1 and ref.…”

Evaluation of calretinin immunohistochemistry as an additional tool in confirming the diagnosis of Hirschsprung disease

“…False negative AChE results related to patient's age present additional diagnostic difficulty. An absence of characteristic AChE reaction does not exclude HD in neonates within the first 3 weeks of life [4,5]. Immunohistochemical (IHC) techniques provide additional helpful tools for the diagnosis of HD.…”