HIF-1α expression is inversely associated with tumor stage, grade and microvessel density in urothelial bladder...

Urothelial bladder carcinoma (UBC) is the most common urinary tract malignancy. The most important histopathological factors affecting prognosis are cancer stage and grade. Studies show that microvessel density (MVD) reflecting angiogenesis is also associated with clinicopathological features and affects the outcome in UBC. One of the most important regulators of angiogenesis is hypoxia inducible factor 1 (HIF-1). Previous reports describing expression of the HIF-1α subunit in UBC showed unclear and inconsistent results. Our study attempted do evaluate the association between HIF-1α expression and tumor stage, grade, lymph nodes status and MVD in UBC. We performed immunohistochemical staining in 99 UBC cases, including 38 non-muscle invasive (NMIBC) and 61 muscle invasive tumors (MIBC). We observed inverse relationships between HIF-1α immunoreactivity score (IRS) and tumor stage, grade and MVD. Significantly lower HIF-1α IRS values were observed in MIBC and high grade cancers. We found a significant negative correlation between HIF-1α IRS and MVD. These results suggest that HIF-1α pathway is not involved in UBC growth and progression, and that angiogenesis in high grade MIBC is not regulated by HIF-1. Our findings contradict previous reports regarding HIF-1α, MVD and UBC which shows the necessity of additional molecular studies in this field.