PURPOSE: The identification of factors predicting the outcome of stage T1 
high-grade bladder cancer (BC) is a major clinical issue.
METHODS: We performed immunohistochemistry to assess the role of human epidermal 
growth factor receptor-2 (HER-2) and microsatellite instability (MSI) factors 
MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in predicting recurrence and 
progression of T1 high-grade BCs having undergone transurethral resection of 
bladder tumor (TURBT) alone or TURBT + intravesical instillations of bacillus 
Calmette-Guerin (BCG).
RESULTS: HER-2 overexpression was a significant predictor of disease-free 
survival (DFS) in the overall as well as in the two patients' population; as for 
progression-free survival (PFS), it was significant in the overall but not in 
the two patients' population. MLH1 was an independent predictor of PFS only in 
patients treated with BCG and MSH2 failed to predict DFS and PFS in all 
populations. Most importantly, the higher the number of altered markers the 
lowers the DFS and PFS. In multivariate Cox proportional-hazards regression 
analysis, the number of altered molecular markers and BCG treatment were 
significant predictors (p = 0.0004 and 0.0283, respectively) of DFS, whereas the 
number of altered molecular markers was the only significant predictor 
(p = 0.0054) of PFS.
CONCLUSIONS: Altered expression of the proto-oncogene HER-2 and the two 
molecular markers of genetic instability MLH1 and MSH2 predicted T1 high-grade 
BC outcome with the higher the number of altered markers the lower the DFS and 
PFS. These findings provide grounds for further testing them in predicting the 
outcome of this challenging disease.