ABSTRACT

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.

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.

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.

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.

Keywords: Endometrium cancer, HIF-1a, hypoxia, angiogenesis