Adenocarcinomas of the bladder are rare, with the diagnosis dependent on exclusion of secondary involvement by direct extension or metastatic spread from other sites. The recent description of an unusual form of urothelial-type mucinous prostatic
adenocarcinoma raises a novel differential diagnosis between
adenocarcinomas of the prostate and bladder, and investigation into the utility of classic prostatic immunohistochemical
antigens in bladder
adenocarcinoma is warranted. We identified 37 primary infiltrating
adenocarcinomas of the bladder, which included signet ring cell
carcinomas (n=11), urachal
adenocarcinomas (n=5), and enteric
adenocarcinoma (n=21). Also included for comparison were 3 cases, each of bladder
villous adenomas and bladder
adenocarcinoma in situ. Tissue microarrays were constructed from each case, with each specimen represented by multiple 1.0-mm cores to assess for
tumor protein heterogeneity. Immunohistochemistry for
prostate-specific antigen (PSA), prostate specific
acid phosphatase (PSAP), P501S (
prostein), and prostate specific membrane
antigen (PSMA) was performed, and moderate to strong immunoreactivity was considered a positive result. Of the 37
adenocarcinomas, all were negative for PSA and PSAP (0/37; 0%). In contrast, a minority of bladder
adenocarcinomas was labeled with the prostate
antigens P501S and PSMA. P501S showed moderate diffuse cytoplasmic staining in 4/37 cases (11%), including 3 enteric-type
adenocarcinomas and 1
mucinous adenocarcinoma. Additionally, 1 case of
adenocarcinoma in situ demonstrated diffuse cytoplasmic staining for P501S. The granular perinuclear staining pattern of P501S typically seen in prostatic
adenocarcinoma was absent in all cases of bladder
adenocarcinoma. PSMA showed diffuse cytoplasmic staining in 4/37 (11%) infiltrating
adenocarcinomas (including 1 signet ring
carcinoma and 3 enteric-type
adenocarcinomas), and in 1 case of
adenocarcinoma in situ. Membranous PSMA staining was evident in an additional 3
tumors, 1 urachal
mucinous adenocarcinoma, 1 nonurachal mucinous and signet ring cell
adenocarcinoma, and 1 nonurachal
villous adenoma. In conclusion, although all cases of bladder
adenocarcinoma examined were negative for PSA and PSAP, the surprising finding that a subset of invasive and in situ
adenocarcinomas of the bladder demonstrated immunoreactivity for P501S and PSMA should warrant caution when using these markers in differentiating prostatic from bladder
adenocarcinomas. The lack of granular perinuclear staining for P501S and the absence of membranous PSMA staining both favor a bladder
adenocarcinoma, although rare cases of
villous adenoma and
adenocarcinoma did show PSMA membranous staining indistinguishable from that seen in
prostate cancer. Although the novel
antigens P501S and PSMA are fairly specific and more sensitive in the differential diagnosis of prostate and urothelial
carcinoma, care must be taken when
adenocarcinomas of the bladder are considered within this differential diagnosis.