Association between immunohistochemical expression of vascular endothelialgrowth factor (VEGF), VEGF-expressing neuroendocrine-differentiated tumor cells, and outcome in prostate cancer patients subjected to watchful waiting

Tumor growth is dependent on angiogenesis, which is thought to be controlle d by angiogenic factors, Therefore, the immunoreactivity of the angiogenic cytokine vascular endothelial growth factor (VEGF) was semiquantitatively s cored in archival prostate tumors obtained at diagnosis in 221 patients fol lowed expectantly. At diagnosis, 125 patients suffered from clinically loca lized disease, Median length of follow-up was 15 years, and 57% of the pati ents eventually died of prostate cancer. All of the tumors exhibited cytopl asmic staining for VEGF. The staining intensity was weak in 47 tumors and m oderate and strong in 107 and 67, respectively. VEGF expression was signifi cantly correlated with microvessel density (MVD; median, 43; range, 16-151; P = 0,014), increasing T-classification (P = 0,001), dedifferentiation (P < 0,001), and disease-specific survival (P = 0,013), Strongly VEGP-immunore active, neuroendoerine-differentiated (NE) tumor cells were observed in 125 tumors. NE expression was significantly correlated with increasing MVD, in creasing T-classification, dedifferentiation and survival (all, P < 0,001), MVD and NE tumor cell expressions were significant variables in a multivar iate analysis that included patients with clinically localized prostate can cer only. VEGF and NE expression mere significantly correlated with MVD cli nical characteristics, and disease-specific survival. NE expression was a s ignificant prognostic marker in localized prostate cancer patients, whereas the applied semiquantitatively scoring of VEGF expression was inadequate t o make this growth factor provide any additional prognostic information, Mo reover, the significant VEGF expression of NE tumor cells suggests an addit ional important character of these cells in the involvement in disease prog ression.