Combined expression of S100A4 and Annexin A2 predicts disease progression and overall survival in patients with urothelial carcinoma.

OBJECTIVES

To determine the expression patterns and prognostic value of S100A4 and Annexin A2 for urothelial carcinoma of the urinary bladder.

METHODS AND MATERIALS

Immunohistochemical staining for S100A4 and Annexin A2 was performed in 315 archived radical cystectomies and 63 normal specimens. The immunoreactivity of these proteins was correlated to evaluate their clinical significance as prognostic factors.

RESULTS

Protein levels of S100A4 and Annexin A2 were up-regulated in urothelial carcinoma compared with adjacent nontumor tissues. The increased expressions of S100A4 and Annexin A2 were associated with invasion depth, lymph node metastasis, and distant metastasis (P<0.05). High expression of S100A4 correlated with expression of Annexin A2. These alterations in expression were also associated with greater risk of disease progression and decreased chance of carcinoma-specific survival. Further multivariate analysis suggested that expressions of S100A4 and Annexin A2 were independent prognostic indicators for overall survival in urothelial carcinoma. The patients with S100A4-positive/Annexin A2-positive carcinomas presented the lowest 5-year survival rate compared with the other 3 groups.

CONCLUSIONS

S100A4 and Annexin A2 proteins could be useful prognostic markers to predict tumor progression and prognosis in urothelial carcinoma. The expression patterns of S100A4/Annexin A2 interaction correlated well with the pathologic stage, disease progression, and carcinoma-specific survival. This finding could aid in identifying more biologically aggressive carcinomas and thus patients who might benefit from more intensive adjuvant therapy.