To gain more detailed insight into the histogenesis of primary nonurachal
adenocarcinomas and signet ring cell
carcinomas of the urinary bladder, we analyzed by immunohistochemistry the expression of a broad panel of
proteins, associated with cell differentiation (pS2
peptide, MUC5AC, MUC6,
spasmolytic polypeptide,
cyclooxygenases-1 and -2,
caveolin-1), and of various novel known or candidate
tumor suppressors (14-3-3 sigma, SYK, PTEN,
maspin). Included were 12
adenocarcinomas admixed to urothelial
carcinomas, 10 pure
adenocarcinomas and 5 signet ring cell
carcinomas. As the most important finding, the majority of signet ring cell
carcinomas and three quarters of the
adenocarcinomas (72.7%) expressed the pS2
peptide, and nearly half of the
adenocarcinomas (45.5%) as well as most of the signet ring cell
carcinomas were observed to secrete the MUC5AC
apomucin. Since expression of both
proteins was absent in the normal nonneoplastic urothelium, their
tumor-associated appearance is regarded as a neoexpression or reexpression, respectively, of normally cryptic
antigenic determinants, and is assumed to be involved in the phenotypical formation of vesical
adenocarcinomas, including signet ring cell
carcinomas. The expression of both pS2 and MUC5AC in variants of urothelial
carcinomas with a glandular differentiation and an extracellular mucus production support the concept that
adenocarcinomas may histogenetically develop from preexistent TCC.
Adenocarcinomas which secrete the pS2
peptide and the MUC5AC
glycoprotein are proposed to be subclassified as
adenocarcinomas of the intestinal type, as distinguished from those of the common type lacking an expression. The tumor suppressor genes showed a loss of
protein expression in
adenocarcinomas, ranging from 54.5% (14-3-3 sigma), to 31.8 (PTEN), 27.3% (SYK) and 18.2% (
maspin). Similar expression profiles in the coexistent urothelial
carcinomas argue against a specific involvement of these genes during the morphogenesis of
adenocarcinomas.