Expression of PAX8 in nephrogenic adenoma and clear cell adenocarcinoma of the lower urinary tract: evidence of related histogenesis?

Recent evidence has showed that nephrogenic adenoma is a true "nephrogenic" lesion derived from the proliferation of exfoliated and implanted renal tubular cells in the urinary tract, a process that closely resembles the formation of endometriosis. This new concept has led to the identification of renal transcription factor PAX2 as a diagnostic marker for nephrogenic adenoma. PAX8 is another transcription factor structurally and functionally related to PAX2. Both are cell lineage restricted transcription factors expressed in normal and neoplastic tissues of related origin, including renal tubular cells in both fetal and adult kidneys. In this study, we investigated the expression of PAX8 in nephrogenic adenoma and its mimics. We report here that PAX8 was detected in all nephrogenic adenomas (N=35) and clear cell adenocarcinoma of the lower urinary tract (N=7), but not in prostate adenocarcinoma (N=100), adenocarcinoma (N=9), squamous cell carcinoma (N=5), or urothelial carcinoma (N=48) of the urinary bladder and its variants. PAX8 was neither detected in normal urothelium of the urinary bladder nor in prostate glands and stroma. PAX2 was also detected in 2 of the 7 clear cell adenocarcinomas of the lower urinary tract. We suggest that PAX8 is an additional marker for identifying nephrogenic adenoma. Expression of PAX8 or PAX2 in both nephrogenic adenoma and clear cell adenocarcinoma of the lower urinary tract may indicate a possible related tissue origin for these 2 lesions; both may be derived from proliferating renal tubular cells in the urinary tract. In addition, detection of PAX8 or PAX2 in clear cell adenocarcinoma of the lower urinary tract is helpful in differentiating it from urothelial carcinoma and its variants and adenocarcinomas of the urinary bladder or of the prostate.