Immunohistochemical analysis of chromatin remodeler DAXX in high grade urothelial carcinoma.

Background/Aims The chromatin remodeler DAXX, a predominantly nuclear protein, regulates the status of chromatin organization. The aim of this exploratory immunohistochemical study was to evaluate DAXX protein expression in high grade invasive urothelial carcinoma (UC) of the bladder as a biological regulator of aggressiveness. METHODS: Quantitative analysis was made on DAXX immunostained nuclei in tissue sections from 5 cases of bladder normal urothelium (NU) and 5 cases of bladder pT1 UC. Carcinoma in situ (CIS) and high grade papillary carcinoma (HGPCa) were identified in 2 out of 5 UC cases. RESULTS: The nuclei in UC show an open configuration of the chromatin composed of granules varying in size and distribution and a mean nuclear area 1.7 times greater than that in NU (UC: mean and SD 24.4 +/- 11.4 square microns; NU: 14.8 6.5 square microns. The differences are statistically significant). 70% of the NU nuclei are immunostained, whereas 90% of UC nuclei are positive. The mean gray level value in UC, related to the intensity of nuclear immunostaining, is lower than in NU by a factor of 0.94 (UC: mean and SD 100 +/- 15; NU: 106 +/- 15. The differences are statistically significant). In part icular, the value in the nuclei adjacent to the stroma in UC is slightly lower than in the intermediate cell layers by factor of 0.98, whereas in NU it is slightly greater by a factor 1.02 and 1.04 compared to the intermediate and superficial cell layers. The values in CIS and HGPCa are similar to those in UC. CONCLUSIONS: The quantitative immunohistochemical analysis shows an altered protein expression of chromatin remodeler DAXX in UC and in its preinvasive phases, when compared to NU. DAXX evaluation, if associated with markers related to global D NA methylation and histone acetylation, could be used in clinical practice as a marker of aggressiveness.