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.
[Show abstract][Hide abstract] ABSTRACT: Rectal suction biopsy (RSB) is the gold standard diagnostic procedure for disorders of bowel motility. This study describes
our experience with RSB stained with histochemistry as the first diagnostic approach in a large series of patients presenting
with chronic constipation. Between 1993 and 2005, 766 children underwent RSB for persistent chronic constipation. The specimens
were snap frozen, sectioned and stained with conventional hematoxylin and eosin (H&E) and with nicotinamide adenine dinucleotide
phosphate diaphorase (NADPH-d) and acetylcholinesterase (AChE) histochemical stainings. Adequate amount of submucosa was present
in 655 (85.5%) out of 766 cases and formed the basis of this study. RSB in 540 (82%) patients were reported as normal. Hirschsprung’s
disease was found in 47 (7.2%) patients with characteristic features of absence of ganglion cells, increased AChE activity
in the lamina propria and muscularis mucosae, thick nerve fibers in the submucosa, and a lack of NADPH-d-positive fibers in
muscularis mucosae. RSB in 59 (9%) patients presented features of intestinal neuronal dysplasia such as submucosal hyperganglionosis,
giant ganglia, ectopic ganglia and increased AChE activity in lamina propria. Hypoganglionosis was suspected in nine (1.3%)
children because of sparse or absent ganglion cells and low AChE and NAPDH-d activity in muscularis mucosae. Three patients
(0.4%) developed bleeding following RSB, requiring diathermy of the bleeding point. Thus, we conclude that RSB is a simple
and safe method when used as the first diagnostic approach in patients with chronic constipation. The combination of two histochemical
stainings techniques provides a high level of accuracy in the diagnosis of intestinal dysganglionosis.
Pediatric Surgery International 07/2008; 24(7):785-792. DOI:10.1007/s00383-008-2173-1 · 1.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aberrations of cholinesterase (ChE) genes and the variation of ChE activity in cancerous tissues prompted us to investigate the expression of ChEs in colorectal carcinoma. The study of 55 paired specimens of healthy (HG) and cancerous gut (CG) showed that acetylcholinesterase (AChE) activity fell by 32% and butyrylcholinesterase (BuChE) activity by 58% in CG. Abundant AChE-H, fewer AChE-T, and even fewer AChE-R and BuChE mRNAs were observed in HG, and their content was greatly diminished in CG. The high level of the AChE-H mRNA explains the abundance of AChE-H subunits in HG, which as glycosylphosphatidylinositol (GPI)-anchored amphiphilic AChE dimers (G
2A) and monomers (G
1A) account for 69% of AChE activity. The identification of AChE-T and BuChE mRNAs justifies the occurrence in gut of A12, G
4H and PRiMA-containing G
4A AChE forms, besides G
4A and G
1H BuChE. The down-regulation of ChEs might contribute to gut carcinogenesis by increasing acetylcholine availability and overstimulating muscarinic receptors.
Cellular and Molecular Life Sciences CMLS 10/2006; 63(18):2175-82. DOI:10.1007/s00018-006-6231-3 · 5.81 Impact Factor
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