Email updates

Keep up to date with the latest news and content from Diagnostic Pathology and BioMed Central.

Open Access Research

Immunohistochemical analysis of chromatin remodeler DAXX in high grade urothelial carcinoma

Antonio Zizzi1, Maria Alessandra Montironi2, Roberta Mazzucchelli1, Marina Scarpelli1, Antonio Lopez-Beltran3, Liang Cheng4, Nicola Paone2, Paolo Castellini2 and Rodolfo Montironi1*

Author affiliations

1 Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Via Conca 71, 60126, Torrette Ancona, Italy

2 Department of Industrial Engineering and Mathematical Sciences (DIISM), Polytechnic University of the Marche Region, Ancona, Italy

3 Department of Surgery, Cordoba University Medical School, Cordoba, Spain

4 Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN USA

For all author emails, please log on.

Citation and License

Diagnostic Pathology 2013, 8:111  doi:10.1186/1746-1596-8-111

Published: 2 July 2013

Abstract

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 particular, 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 DNA methylation and histone acetylation, could be used in clinical practice as a marker of aggressiveness.

Virtual slides

The virtual slides for this article can be found here:

http://www.diagnosticpathology.diagnomx.eu/vs/1398457297102379 webcite

Keywords:
Urothelium; Urothelial carcinoma; Chromatin remodeler DAXX; Biological regulator