Female urethral adenocarcinoma: Immunohistochemical evidence of more than 1 tissue of origin

Purpose: Urethral adenocarcinoma is a rare malignancy whose origin remains controversial. The monoclonal antibody mAbDas1 (formerly 7E12H12) was devel oped against a unique colonic epithelial epitope and is reactive in areas o f intestinal metaplasia. Recently the antibody was shown to react in cystit is glandularis as well as adenocarcinoma of the bladder, suggesting that cy stitis glandularis may be the precursor of bladder adenocarcinoma. We exami ned urethral adenocarcinomas and benign urethral specimens using mAbDas1 to determine whether it could provide insight into their histogenesis. Materials and Methods: Archival tissue from 12 cases of primary female uret hral adenocarcinoma and urethral specimens of inflamed urethral mucosa, ure thritis glandularis and transitional cell carcinoma was studied. Immunohist ochemical analysis of formalin fixed, paraffin embedded archival tissue was done using the monoclonal antibody mAbDas1. Tumors were also evaluated wit h a prostate specific antigen (PSA) polyclonal antibody as previous studies have noted PSA reactivity in these tumors. Results: Of the 12 cases 9 were columnar/mucinous adenocarcinoma, 2 clear c ell adenocarcinoma and 1 a cribriform pattern resembling adenocarcinoma of the prostate. All columnar/mucinous adenocarcinomas reacted positively (6 s trongly and 3 focally) with the mAbDas1 antibody but did not react with the PSA antibody. The tumor with a cribriform pattern reacted strongly with PS A but did not react with mAbDas1. The 2 clear cell adenocarcinomas did not react with either antibody. The benign urethral specimens demonstrated stro ng reactivity to the mAbDas1 antibody in areas of urethritis glandularis bu t normal and inflamed urethral mucosa and transitional cell carcinoma did n ot react. Conclusions: Primary adenocarcinoma of the female urethra arises from more than 1 tissue of origin. Columnar/mucinous adenocarcinomas of the female ur ethra and urethritis glandularis demonstrate consistent reactivity with the mAbDas1 antibody, suggesting that these tumors arise from glandular metapl asia analogous to the potential histogenesis previously demonstrated in the bladder. PSA reactivity occurred in 1 tumor with a cribriform pattern and likely represents origin from Skene's glands. Clear cell adenocarcinomas di d not react with either antibody, suggesting a third possible pathway in th e development of this rare subset of adenocarcinomas.