The detection of PAX8 in human upper urinary tract urothelial carcinoma

Upper urinary tract urothelial carcinomas (UUT-UCs) are defined as malignant neoplasms of the urothelium from the upper urinary tract, including renal calyces, the renal pelvis and the distal ureter. The natural attributes of UUT-UCs differ from those of bladder cancer. The aim of the present study was to investigate PAX8 expression in the normal urothelium and in urothelial carcinomas (UCs) of the upper urinary tract. Immunohistochemistry was conducted in 35 cases of renal pelvic and 30 cases of ureteral papillary UCs and the adjacent normal urothelium respectively. PAX8 mRNA expression was evaluated by RT-PCR in a different set of normal urothelial mucosa of the urinary tract and UUT-UCs. In immunohistochemical studies, the positive rates of PAX8 staining in UCs of the renal pelvis and ureter were 17% and 6.6% respectively, presenting focally positive in most cases, while the positive rates in the adjacent normal epithelia of the pelvis and ureter were 100% and 93% respectively. PAX8 mRNA was detected in all of the tumors and adjacent normal urothelial mucosa specimens of the upper urinary tract. 4 types of PAX8 isoforms, PAX8a, PAX8b, PAX8c and PAX8e, were detected in UUT-UCs in this study. As in bladder cancer, PAX8 expression was highly heterogeneous in terms of the splicing mRNA isoforms, with the different isoforms differentially expressed in the UUT-UCs. Among the 4 types of PAX8 isoforms, the PAX8e isoform was found in almost all UUT-UCs tumor tissues, but the PAX8d isoform was not detected in UUT-UCs that were different from the transcriptional splicing patterns of PAX8 in bladder cancer reported in the literature. In addition, the above 4 types of PAX8 splicing isoforms were simultaneously detected in almost all of the normal mucosal epithelia of the upper urinary tract, which was very different from that of bladder mucosa. Further studies are suggested to reveal whether or not the differences in natural attributes between UCs of the upper and lower urinary tracts are related to their PAX8 transcriptional splicing patterns.