Expression of MUC5AC apomucin in transitional cell carcinomas of the urinary bladder and its possible role in the development of mucus-secreting adenocarcinomas

The histogenesis of primary nonurachal mucus-producing adenocarcinomas of t he urinary bladder including signet ring cell carcinomas remains to be eluc idated, since the normal bladder contains neither columnar nor mucus-secret ing glandular epithelium. Based upon the assumption that adenocarcinomas ma y develop secondarily from pre-existent transitional cell carcinomas (TCC) by a metaplastic process, it was the purpose of the current immunohistochem ical study to analyze whether urothelial carcinomas are capable of secretin g MUC5AC apomucin, using the monoclonal antibody 45M1. This antibody has be en initially demonstrated to strongly react with the mucus-producing column ar cells of the surface gastric epithelium. recognizing a specific epitope located on the peptide core of glycoproteins as major components of mucins. Nine of 64 uniformly differentiated papillary (14.1%) and 5 of 66 nonpapil lary (solid) TCC with a uniform urothelial differentiation (7.6%) expressed the MUC5AC antigen, yielding an overall incidence of 10.8%. Transitional c ell carcinomas with a focally altered cellular and structural differentiati on (squamous cell, pseudoglandular, true glandular and mixed differentiatio n) stained positively in a substantially higher percentage of 43.8% (21 of 48 cases). A positive immunoreactivity was also observed in 3 of 19 mixed t ransitional cell and nonurothelial carcinomas. The tumor-associated resurge nce of normally cryptic MUC5AC antigenic determinants in transitional cell carcinomas is considered as a re-expression of oncofetal antigenicity, prob ably as a result of the embryologic origin of the urinary bladder from the pluripotent tissues of the cloacal endoderm and the mesodermal wolffian duc ts. Our findings may help to better understand the histogenetic development of mucus-secreting vesical adenocarcinomas from pre-existent urothelial ca rcinomas.