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Background  Seventy percent of all bladder tumours tend to recur and need intensive surveillance, and a subset of tumours progress to muscle-invasive and metastatic disease. However, it is still difficult to find the adequate treatment for every individual patient as it is a very heterogeneous disease and reliable biomarkers are still missing. In our study we searched for new target genes in the critical chromosomal region 8p and investigated the potential tumour suppressor gene candidate  MTUS1/ ATIP in bladder cancer.    Methods   MTUS1  was identified to be the most promising deleted target gene at 8p in aCGH analysis with 19 papillary bladder tumours. A correlation with bladder cancer was further validated using immunohistochemistry of 85 papillary and 236 advanced bladder tumours and in functional experiments. Kaplan-Meier analysis and multivariate Cox-regression addressed overall survival (OS) and disease-specific survival (DSS) as a function of  MTUS1/ ATIP expression. Bivariate correlations investigated associations between  MTUS1/ ATIP expression, patient characteristics and histopathology.  MTUS1  expression was analysed in cell lines and overexpressed in RT112, where impact on viability, proliferation and migration was measured.    Results   MTUS1  protein expression was lost in almost 50% of all papillary and advanced bladder cancers. Survival, however, was only influenced in advanced carcinomas, where loss of  MTUS1  was associated with adverse OS and DSS. In this cohort, there was also a significant correlation of  MTUS1  expression and histological subtype: positive expression was detected in all micropapillary tumours and aberrant nuclear staining was detected in a subset of plasmocytoid urothelial carcinomas.  MTUS1  was expressed in all investigated bladder cell lines and overexpression in RT112 led to significantly decreased viability.    Conclusions   MTUS1  is a tumour suppressor gene in cultured bladder cancer cells and in advanced bladder tumours. It might represent one new target gene at chromosome 8p and can be used as an independent prognostic factor for advanced bladder cancer patients. The limitation of the study is the retrospective data analysis. Thus, findings should be validated with a prospective advanced bladder tumour cohort.

Loss of MTUS1/ATIP expression is associated with adverse outcome in advanced bladder carcinomas: data from a retrospective study