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Hypoxia-inducible factor-1alpha (HIF-1alpha) is a critical regulatory protein of cellular response to hypoxia. In this study, we evaluated the relationship of HIF-1alpha with clinicopathologic parameters such as tumor stage and grade, as well as angiogenic profile and proliferation index. The immunoreactivity of HIF-1alpha was assessed in 70 cases of primary bladder urothelial carcinoma. Vascular endothelial growth factor (VEGF) and microvessel density (MVD) were used to evaluate the angiogenic profile. MVD was calculated by immunohistochemical staining of endothelial cells with CD34. Proliferation index was determined by the percentage of Ki-67 nuclear staining in tumor cells. There was a significant relationship between HIF-1alpha immunoreactivity and stage, as well as histologic grade of the tumor (P < 0.001). HIF-1alpha immunoreactivity was also closely related to VEGF expression (P < 0.001), MVD (P = 0.002) and proliferation index (P < 0.001). VEGF, MVD and proliferation index were found to be closely related to tumor stage and histologic grade. There was no correlation between HIF-1alpha immunoreactivity and lamina propria (P = 0.13), muscularis propria (P = 0.009) or vascular invasion (P = 0.1). In this study, HIF-1alpha expression was found to be closely related to prognostic parameters in bladder urothelial carcinoma. For this reason, it may be a useful marker to determine the prognosis and to choose the appropriate treatment modality.

Objective: Smooth muscle fibres are found within the superficial lamina propria of urinary bladder (Muscularis Mucosa). These muscle fibres of muscularis mucosa should be distinguished from the muscularis propria in cases with urothelial carcinoma, because the depth of infiltration affects prognosis and therapy modalities. The aim of the present study was to evaluate whether the presence of vascular plexus is a criterion for muscularis mucosa and to distinguish it from muscularis propria in urinary bladder biopsies and transurethral resection specimens., Materials and Methods: Hematoxylin-Eosin and Masson-Trichrome stained slides of 54 cases with urothelial carcinoma were reviewed., Results: In all cases (100%), thick walled vessels were observed within the lamina propria of urinary bladder. Smooth muscle layer of lamina propria was seen in 48 of 54 cases (88.8%), and these smooth muscle fibres were co-existed with thick walled vessels. In invasive urothelial carcinoma; thin smooth muscle fibres and thick walled vessels were seen within the lamina propria in 22 of 24 cases (91.7%). There were two cases (8.3%) including only vessels in small biopsies of invasive urothelial carcinoma cases. In cases with non-invasive urothelial carcinoma; muscle fibres of muscularis mucosa and vessels were found within the lamina propia in 26 of 30 cases (86.7%). In this group, muscle fibres were not detected in 4 cases (13.3%)., Conclusion: Muscularis mucosa can be detected histologically in urinary bladder biopsies and TUR materials. We emphasize that the presence of vascular network is a useful criterion to determine muscularis mucosa of urinary bladder, even in the absence of muscle fibres.