Angiogenetic factors in urological tumors
Fujiyama C., Masaki Z., Jones A., Turner K., Cranston D., Harris A.
Angiogenesis is a prerequisite for tumor growth and metastasis. We have previously reported that high expressions of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP) within bladder tumors are associated with poor prognosis. To investigate the role of angiogenic factors more clearly in the assessment of patients with other urological tumors, we studied these factors in testicular tumors and prostate cancer. Paraffin sections were assessed immunohistochemically from 51 patients with clinical stage I germ cell tumors of the testis (28 cases of seminoma, 23 cases of teratoma) treated by orchidectomy and surveillance only. Sections were analysed for microvascular density (MVD), and expressions of the angiogenic factors VEGF and thymidine phosphorylase (TP). In addition, in the seminoma cases, the presence of the lymphangiogenic factor VEGF-C and its corresponding receptor VEGFR-3 was examined. Serum from 48 patients with prostate cancer (16 with local disease, 32 with metastatic disease), 9 with benign prostatic hyperplasia and 21 healthy controls was assayed for VEGF using a commercial kit. Teratoma specimens had a significantly higher mean MVD (85, 26∼163) than either seminoma (37, 16∼91) or normal specimens (26, 18∼30). Teratoma specimens also had a significantly higher VEGF and TP expression than either seminoma or normal specimens. There was no significant correlation between either MVD or VEGF and relapse-free survival. VEGF-C and VEGFR-3 were detected in one third to half of the cases. The mean serum VEGF level was significantly higher in patients with hormone-escaped prostate cancer than in all other groups. There was no significant difference in serum VEGF level during either response to or escape from hormonal therapy. Marked differences between normal testis and tumors implicate angiogenesis in the biology of germ cell tumors of the testis. The significantly higher VEGF level in patients with hormone-escaped prostate cancer suggests a role in the pathogenesis of advanced cancer. Although angiogenic factors are not prognostic in either series of these studies, the detection of factors involved in lymphangiogenesis in testicular tumors and prostate cancer, which initially metastasize primarily to the lymph nodes, is warranted in the search for further prognostic indicators and therapeutic targets.