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

Abstract

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.

Identification of Epigenetic Interactions between miRNA and Gene Expression as Potential Prognostic Markers in Bladder Cancer

“…Nevertheless, the relation between tumor stage and HIF1α in BC is unclear [ 41 , 42 ]. Our study showed an inverse relationship between HIF1α expression and tumor stage, with significantly lower HIF1α levels in high stages of pT2–pT4, a finding in agreement with [ 43 ]. Furthermore, miR-138 was found to suppress the proliferation and invasion of cancer cells by inhibiting HIF1α [ 29 ].…”

Influence of the grade and invasiveness of bladder cancer on disease course severity in patients with bladder tamponade resulting from a bleeding bladder cancer

“…[ 11 ] A number of other authors reported that higher microvessel density is significantly associated with the advanced T stage and high histological grade of bladder tumors. [ 12 - 14 ] Increased vascularization of higher-grade and more invasive tumors could potentially lead to more profuse bleeding, more severe anemia, and a greater need for transfusions, and consequently to a more severe disease course and a longer hospitalization.…”

Urine-Based Regenerative RNA Biomarkers for Urinary Bladder Wound Healing

“…It is associated with human lower urinary tract symptoms [20], IC/PBS and neurogenic bladder [19,25]. In bladder cancer, HIF-1α expression is negatively correlated with tumor stage, grade and microvessel density [26].…”