Cancers of the Genitourinary Tract

Up till now, only the study by Olivarez et al. (89) evaluated the clinical significance of neovascularization in testicular germ cell tumors. They assessed vascularity of 65 primary tumors of patients with clinical stage A, using the factor VIII-RA.

After surgery, 43 patients had pathologic involvement of the retroperitoneal lymph nodes (histolgic stage B); the other 22 patients had no metastasis in the lymph nodes (pathologic stage A). Retrospectively, the authors found that quantitation of microvessel density was significantly predictive of occult metastatic disease on univariate analysis. However, in the logistic regression multivariate analysis, only absence of yolk-sac tumor elements retained significance in predicting pathological stage B.

Viglietto et al. (90) analyzed the expression of mRNA VEGF in human germ cell tumors, and found that more than 80% of the tumors were VEGF-positive, and that high levels of its expression are associated with high vascularization.

Much more information is available on the association of microvessel density with stage disease in prostatic cancer (91-98) (Table 5). Wakui et al. (91) first reported that the blood capillary density ratio, as assessed by a marker antivimentin, was predictive of bone marrow metastasis. All the other authors (91-98) who performed the subsequent studies confirmed that the degree of vascularization of the primary tumor is predictive of advanced pathologic stage or metastasis. Regarding invasive bladder carcinoma, all the published studies evaluating the prognostic value of microvessel density found that it is a significant and independent prognostic indicator (99-101). Grossfeld et al. (101) also assessed the expression of p53 protein and thrombospondin-1, and found that microvessel density counts were significantly associated with both the above biological markers.

Several authors also evaluated the expression of angiogenesis factors, such as VEGF, fibroblast growth factors (FGFs), TP, hepatocyte growth factor (or scatter factor), and pleiotrophin in human cancer of the bladder (reviewed in ref. 102). The most important factors mediating angiogenesis in such a tumor seem to be acidic and basic FGFs, VEGF, and TP. A differential expression of VEGF and TP in superficial and invasive cancers suggests that different angiogenic pathways may occur at different stages of this neoplasm.

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