OVER EXPRESSION OF PLATELET-DERIVED ENDOTHELIAL CELL GROWTH FACTOR/THYMIDINE PHOSPHORYLASE IN PATIENTS WITH INTERSTITIAL CYSTITIS AND BLADDER CARCINOMA

Abstract

We examined whether the expression of angiogenic factors, such as platelet-derived endothelial cell growth factor/thymidine phosphorylase (PDEGF/TP) and transforming growth factor-beta, in bladder tissue correlates with the severity of symptoms, such as urinary urgency and bladder pain, in patients with bladder carcinoma and interstitial cystitis. Bladder biopsy was performed in 32 patients with bladder carcinoma, including 19 with interstitial cystitis and 3 controls. Immunohistological staining for PDEGF/TP, transforming growth factor-beta and CD44 was performed in bladder specimens. PDEGF/TP in bladder tissues was also measured by enzyme-linked immunosorbent assay to examine the correlation of the expression of this factor with painful symptoms in patients with bladder carcinoma or interstitial cystitis. Immunohistochemical staining showed that PDEGF/TP stained in the submucosal layer beneath the basement membrane in bladder tissues of patients with interstitial cystitis and peritumoral areas of those with bladder carcinoma. In addition, PDEGF/TP, transforming growth factor-beta and CD44 stained in the same submucosal region and staining was observed at deeper submucosal levels in interstitial cystitis cases with severe rather than mild bladder pain. Quantitative analyses revealed that mean PDEGF/TP expression plus or minus standard deviation in tumor tissues of 10 patients with bladder carcinoma and pain was significantly higher than in tumor tissues of 22 with asymptomatic bladder carcinoma (129.3 +/- 70.7 versus 37.6 +/- 29.2 units per mg. protein). The mean expression of PDEGF/TP in peritumoral mucosa of patients with bladder carcinoma and pain was also significantly higher than in those with asymptomatic bladder carcinoma (75.5 +/- 42.1 versus 12.6 +/- 5.4 units per mg. protein). For interstitial cystitis mean expression in 6 patients with severe bladder pain was significantly higher than in 13 with moderate pain (79.2 +/- 59.2 versus 16.6 +/- 17.5 units per mg. protein). Mean expression in bladder tissues of controls was less than 2.3 units per mg. protein. These results suggest that angiogenic factors, such as PDEGF/TP and transforming growth factor-beta, may be involved in the inflammatory process to induce painful symptoms in patients with interstitial cystitis or bladder carcinoma. Proteoglycans such as CD44 may contribute to the presentation of these soluble angiogenic factors at the inflammation site.