Altered expression of alpha-smooth muscle isoactin in Hirschsprung's disease

To analyze the expression of smooth muscle actin (SMA) contractile proteins in the intestinal muscle of patients with Hirschsprung's disease.

A total of 56 colonic whole-wall specimens were tested with immunohistochemistry and monoclonal antibodies directed against, respectively, alpha and pan (alpha and gamma) SMA.

The study included both aganglionic and dilated normoganglionic colonic samples from 29 children who had undergone definitive surgery for Hirschsprung's disease. Morphologically normal (n = 6) and dilated colons (n = 5) from 11 patients suffering from conditions unrelated to Hirschsprung's disease served as controls.

The alphaSMA immunostaining showed a pattern identical to normal controls in all the aganglionic areas and in 70% of the normoganglionic segments. In contrast, a lack of alphaSMA expression confined to the circular muscle cells was observed in 30% of the normoganglionic specimens and in the five dilated control specimens. The same areas showed a faintly reduced immunoreactivity with the antibody to pan SMA, consistent with the absence of alpha-isoactin, but implying the presence of gamma-isoactin. In the Hirschsprung's disease cases, the absence of alphaSMA expression at the time of surgery was associated with the occurrence of long-term postoperative motility problems (p<.01).

These data suggest that alphaSMA expression defect in Hirschsprung's disease may be acquired and related to chronic colonic obstruction and subsequent dilatation. The observed changes correlate with disturbances of peristalsis and could be used to assess the risk of intestinal dysmotility frequently reported after surgical removal of the aganglionic bowel.