Expression of angiopoietin‐1 and ‐2, and its clinical significance in human bladder cancer

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Abstract
OBJECTIVE: To investigate the relationship between angiopoietin‐1 and ‐2 expression and the clinicopathological variables and clinical outcome in patients with bladder cancer treated by surgical resection, as both have been recently identified as antagonistic angiogenic factors which regulate tumour growth.MATERIALS AND METHODS: The expression of angiopoietin‐1 and ‐2 were assessed by immunohistochemistry in tissue sections from 52 transitional cell carcinomas of the bladder (33 grade 1, 15 grade 2, four grade 3, including two associated with carcinoma in situ; 22 were stage Ta, 19 T1 and 11 T2 tumours). Normal bladder specimens were also resected during each operation as controls. The expression angiopoietins were related to the clinicopathological variables of the tumours.RESULTS: Positive immunostaining was detected in 18 samples (35%) for angiopoietin‐1 and in 23 (44) for angiopoietin‐2. There was no significant difference in survival according to tumour angiopoietin‐1 status in the patients, but in contrast the overall survival of patients with angiopoietin‐2‐positive tumours was significantly lower than for those with angiopoietin‐2‐negative tumours (P < 0.05). Positive angiopoietin‐2 expression was significantly correlated with histological grade (P = 0.026), histological stage (P = 0.009) and poor prognosis (P < 0.05). On multivariate analysis, positive angiopoietin‐2 expression was an independent negative predictor for survival (P = 0.042).CONCLUSIONS: These results suggest that angiopoietin‐2 overexpression is associated with tumour progression, thereby indicating a poor prognosis for some patients treated by surgical resection for bladder carcinoma.