Mucin gene expression in human urothelium and in intestinal segments transposed into the urinary tract

Purpose: The repertoire of mucin (MUC) gene expression in the normal human urothelium is poorly defined and the alterations in MUC gene expression fol lowing transposition of intestinal segments into the urinary tract has not previously been studied. The aims of this study were to define MUC gene exp ression in the normal human urothelium; and in transposed intestinal segmen ts. Materials and Methods: Non-isotopic in-situ hybridization was carried out u sing eight digoxigenin labeled oligonucleotide mucin gene probes (MUC 1 - 7 ). Immunohistochemistry using NCL-MUC1 and NCL-MUC2 monoclonal antibodies w as performed on sections of paraffin-embedded tissues. Twenty-seven patient s were investigated (normal human urothelium, n = 6; transposed ileal segme nts, n = 14 and normal ileal controls, n = 7). Results: MUC1 and MUC4 were the predominant mucin genes expressed in the no rmal urothelium with MUC3 being expressed in a third of cases studied; MUC2 , 5AC, 5B, 6 and 7 were not expressed. Despite the morphological changes se en in transposed ileal segments, MUC2 and MUC3 continued to be expressed in these segments albeit in a disorganised fashion. Both MUC1 and MUC4 were u p-regulated in transposed ileal segments, genes expressed by the normal hum an urothelium. All eight mucin genes were expressed in an area of pyloric-t ype metaplasia found in one transposed ileal segment. In patients with clam enterocystoplasty there was evidence of increasing up-regulation of MUC2, 3, 4 and 5AC expression in the urothelium toward the anastomotic site. Conclusion: Transposition of ileal segments into the urinary tract results in up-regulation of MUC1 and MUC4, the predominant MUC genes expressed in t he human bladder. The clinical implication of the up-regulation of some MUC genes toward the anastomotic site in patients with an enteroplasty and the aberrant expression of MUC5AC - MUC7 by transposed segments is at present unclear.