Background: We determined the tumor-associated macrophage (TAM) count to investigate its importance in predicting clinical outcome or prognosis in patients with bladder cancer. Methods:The TAM count and microvessel count (MVC) were determined immunohistochemically in 63 patients with bladder cancer, including 40 superficial bladder cancers and 23 invasive bladder cancers. To examine the relationship between TAM count and clinical outcome or prognosis in bladder cancer, cystectomy rates, distant metastasis rates, vascular invasion rates and 5 year survival rates were compared between patients with low (< 67) and high (≥ 67) TAM counts. Results:The TAM count in invasive bladder cancers (154.22 ± 11.98) was significantly higher than in superficial bladder cancers (49.05 ± 7.76; P < 0.0001). The MVC in invasive bladder cancers (71.55 ± 10.44) was also significantly higher than in superficial bladder cancers (47.02 ± 5.57; P < 0.05). There was a positive correlation between TAM count and MVC (r = 0.30; P = 0.02).Immunohistochemical staining using CD68/horseradish peroxidase monoclonal antibody showed more infiltrating cells in invasive than superficial bladder cancers. Patients with a high TAM count (≥ 67) showed significantly higher rates of cystectomy, distant metastasis and vascular invasion than those with a lower TAM count (< 67). The 5 year survival rate estimated using the KaplanMeier method was significantly lower in patients with a high TAM count than in those with a low TAM count (P < 0.0001). Conclusions:Our results suggest that determination of TAM count in bladder cancer tissues is of value to predict the clinical outcome or prognosis and to select appropriate treatment strategies in patients with bladder cancer.

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Background : Adrenomedullin (AM) has pluripotent activities and is involved in the regulation of vasomotor tone, cell differentiation and embryogenesis. However, the expression and pathophysiological role of AM has not been determined in human renal cell carcinoma (RCC). Methods : Twenty-six RCC specimens and three cultured human RCC cell lines (A498, SN12C and KPK-13) were analyzed. Expression of AM was determined by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis. The correlation between AM expression and microvessel count (MVC) in RCC specimens was examined to determine if AM plays a role in tumor angiogenesis. The correlation between the expression of AM and vascular endothelial growth factor (VEGF) was also investigated. Lastly, the effect of hypoxia upon the mRNA expression of AM, VEGF and hypoxia inducible factor-1 (HIF-1) by RCC cell lines was determined. Results : Immunohistochemistry indicated that AM and VEGF were primarily localized in the cytosol of RCC cells. AM and VEGF mRNA were detected in all RCC specimens and cultured RCC cell lines analyzed by RT-PCR. There was a positive correlation between AM mRNA expression and MVC ( r = 0.516, P = 0.0062), and between VEGF mRNA expression and MVC ( r = 0.485, P = 0.0111). We also observed a positive correlation between AM mRNA expression and VEGF mRNA expression ( r = 0.552, P = 0.0029). Hypoxia significantly induced AM and VEGF mRNA expression, although the increase of the AM mRNA level (10.6-26.7 fold) was markedly greater than that of the VEGF mRNA level (1.5-1.9 fold). Conclusion : These results suggest that hypoxia-induced AM plays a part in tumor angiogenesis in conjunction with VEGF and facilitates human RCC growth under hypoxic conditions.

Multi-drug resistance associated protein as well as P-glycoprotein mediated multi-drug resistance may be induced after chemotherapy for bladder tumors. However, the presence of P-glycoprotein before chemotherapy does not predict clinical outcome in patients with bladder cancer.