The investigation of tumoral angiogenesis with HIF-1 alpha and microvessel density in women with endometrium cancer

Abstract

Objective: Hypoxia inducible factor 1 alpha (HIF-1α) is a nuclear protein upregulated in response to reduced cellular oxygen concentration which therefore acts as a marker for hypoxia. The aim of this study was to determine tumoral angiogenesis with immunohistochemical markers in endometrium cancer and its relation with stage, grade, survival rates and other prognostic factors. Material and Methods:Using the database in our Gynecologic Oncology clinic, we selected 94 patients who were diagnosed with endometrial cancer and underwent primary surgery at our institution between 2001 and 2010. Tissue microarrays believed to demonstrate the optimum part of the tumor were reprepared from the paraffin blocks. Angiogenesis and microvessel density (MVD) were investigated with the aid of HIF-1α and CD34 antibodies.Results: High expression of HIF-1α was significantly more frequent in advanced grade endometrial cancers (p=0.044). HIF-1α expression was highly correlated with CD34 expression in the tumor cells (p<0.001). However lack of relation among stage, overall survival rates and histological types were analyzed with HIF-1α. When we compared HIF-1α positive and negative cases with cervical, adnexial, lymphovascular and myometrial invasion, there was no difference between these groups. MVD was evaluated with CD34 and it was remarkable and significantly different on advanced grade tumors (r=0.268; p=0.009). A similar significant difference was observed between the high expression of CD34 and type II endometrial cancer histology (p<0.001). However, there was no relationship between the MVD and stage or survival rates. Conclusion:High expression of HIF-1α is associated with tumoral angiogenesis in endometrial adenocarcinomas. Further studies targeting HIF-1α for disrupting mechanisms essential for tumor growth in endometrium cancer will be significant investigations in the future. (J Turkish-German Gynecol Assoc 2012; 13: 37-44) Key words: Endometrium cancer, HIF-1α, hypoxia, angiogenesis Received: 21 April, 2011 Accepted: 3 December, 2011 Amaç: Hipoksi ile indüklenen faktör-1α (HIF-1 α) bir nükleer proteindir ve azalan hücre içi oksijen konsantrasyonuna cevap olarak regüle edilir. Bu nedenle bir hipoksi belirteci gibi görev yapar. Bu çalışmanın amacı endometrium kanserli olgularda tümör anjiogenezini immunohistokimyasal belirteçler ile incelemek ve evre, derece ve sağkalım gibi prognostik faktörlerle olan bağlantısını aydınlatmaya çalışmaktır.

Intravoxel Incoherent Motion Combined With Dynamic Contrast‐Enhanced Perfusion MRI of Early Cervical Carcinoma: Correlations Between Multimodal Parameters and HIF‐1α Expression

“…A possible explanation is that tumor hypoxia induces the overexpression of HIF-1α, which is associated with a higher MVD. 31,32 We also found that the tumor with rich stroma had a higher HIF-1α expression. The previous study by us 13 showed that the tumor with rich stroma had a higher D value.…”

“…In addition, this study showed that the high HIF‐1α expression group had higher MVD than the low‐expression group. A possible explanation is that tumor hypoxia induces the overexpression of HIF‐1α, which is associated with a higher MVD . We also found that the tumor with rich stroma had a higher HIF‐1α expression.…”

Hypoxia Inducible Factor-1alpha (HIF-1A) plays different roles in Gallbladder Cancer and Normal Gallbladder Tissues

“…These findings were consistent with previous reports in tumors. MVD was higher in nuclear HIF-1A expression, and nuclear HIF-1A determined the functional activity of the HIF-1A complex 35 , 36 . In normal gallbladder tissues, we found that MVD in cytoplasm HIF-1A + /nuclear HIF-1A - subgroup was significantly higher than that of cytoplasm HIF-1A - /nuclear HIF-1A + subgroup.…”

Prognostic Value of Quantitative Perfusion Parameters by Enhanced Ultrasound in Endometrial Cancer

“…Furthermore, perfusion parameters obtained from the TIC analysis during CEUS examination were significantly associated with micro-vessel density (MVD) of endometrial cancer [22]. It was suggested that the MVD is an indirect marker of the intensity of tumor vascularization, which is known to be associated with the progression of endometrial cancer and survival outcome [24,25]. Therefore, perfusion parameters obtained from the TIC analysis during CEUS examination may be associated with prognosis of endometrial cancer.…”