Aim: The aim of this study was to establish the expression and the significance of angiogenic markers in T1 bladder cancer with concomitant carcinoma “in situ”. Introduction: It has been determined that overexpression of hypoxia-inducible factor 1-alpha (HIF-1alfa), vascular endothelial growth factor (VEGF), and vascular endothelial growth factor receptor1 (VEGFR1) correlates with tumor grade, disease progression and recurrence, as well as poor overall survival. Carcinoma in situ (CIS) is frequently seen in conjunction with bladder tumors and represents an additional obstacle for management of T1 bladder cancer patients. Material and Methods: The immunohistochemical expressions of HIF-1alfa, VEGF, and VEGFR1 were evaluated in 295 T1 bladder cancer samples, incorporated in tissue microarrays. HIF1-alpha was assessed through nuclear staining, while the angiogenic profile was estimated through cytoplasmatic positivity of the VEGF and VEGFR1. Microvessels were identified by immunostaining of endothelial cells for CD34 and microvessel density (MVD) was presented as the average number of counted microvesels. Results: After a mean followup of 53 months, we found that T1 bladder cancer patients, who had concomitant carcinoma in situ had worse overall survival (p<0.05), furthermore, those tumor samples less expressed HIF-1alfa (p<0.05), and VEGFR1 (p<0.05). Expression of VEGF, VEGFR1, HIF-1alfa, as well as MVD, did not have significant impact to survival rate and further outcome. Conclusion: Worse overall survival and decreased expression for angiogenic markers in samples with accompanying CIS were established. Estimation of HIF-1alfa and VEGFR1 expression emerged as potential diagnostic supplement, selecting the T1 bladder cancer patients that could require an intensive follow-up.

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