Fig 2: Associations of MTUS1 loss with histopathological parameters in papillary bladder tumours. Significant direct correlation of MTUS1 expression with tumour grade (5A), stage (5B), CK20 (5C) and Ki67 (5D) expression in papillary bladder tumours. MTUS1 loss was associated with decreased malignant potential of the cell as indicated through increased occurrence of low-grade differentiation, non-invasive growth pattern and weak CK20 and Ki67 expression in carcinomas of the IRS0 (MTUS1-deficient) group.

Fig 3: Association of MTUS1 loss with FGFR3 mutations in papillary bladder tumours.FGFR3 mutation analysis in the papillary bladder tumour group. 6A and B show representative examples of FGFR3 wildtype (6A) and mutation R248C (6B) sequences. To assess data integrity we correlated FGFR3 status with tumour stage (6C) and then with MTUS1 expression (6D). We showed that the majority of FGFR3 mutation tumours had a predominantly non-invasive growth pattern compared to FGFR3 wildtype tumours, which showed more invasive phenotypes. FGFR3 mutation where, however, correlated with MTUS1 loss.

Fig 4: Survival curve analysis in the advanced tumour cohort. 8A and B show Kaplan-Meier curves for overall (8A) and disease specific (8B) survival. Patients with positive MTUS1 expression in the tumour (green) have better overall- and disease specific survival, than tumours with MTUS1 expression loss (red). Multivariate Cox-regression analysis (stepwise backward exclusion) for overall (8C) and disease-specific survival (8D) confirmed Kaplan-Meier findings.

Fig 5: Immunohistochemical expression of MTUS1 in papillary bladder tumours. Representative examples of immunohistochemical stainings of papillary bladder carcinomas with anti-MTUS1 antibody. 4A and B show tumours with negative, 4C and D with positive staining. Localization of MTUS1 is in the cytoplasm.