Vasculogenic Mimicry Formation Is Associated with Erythropoietin Expression but Not with Erythropoietin Receptor Expression in Cervical Squamous Cell Carcinoma

BACKGROUND: Vasculogenic mimicry (VM), as an endothelium-independent cancer microcirculation, has been observed in many malignancies including cervical cancer. Erythropoietin (EPO) and erythropoietin receptor (EPO-R) could produce an angiogenic effect to promote cervical squamous cell carcinoma (CSCC) progression. However, the association between VM formation and EPO/EPO-R expression in CSCC is poorly explored. METHODS: Seventy-six paraffin-embedded CSCC samples, 25 high-grade squamous intraepithelial lesion (HSIL) samples, 20 low-grade squamous intraepithelial lesion (LSIL) samples, and 20 normal cervix samples were collected. Immunohistochemistry SP method was performed to detect EPO/EPO-R expression and CD31/periodic acid-Schiff (PAS) double staining was performed to detect VM formation. The associations of EPO/EPO-R and VM with clinicopathological parameters of CSCC were analyzed. The associations between VM formation and EPO/EPO-R expression were also analyzed. RESULTS: The positive expression rates of EPO and EPO-R were gradually increasing along the progression of normal cervix-LSIL-HSIL-CSCC sequence (P<0.05). EPO and EPO-R expression were not significantly associated with clinicopathological parameters of CSCC patients (P>0.05). VM was significantly associated with FIGO stage, lymphovascular space involvement, and lymph node metastasis (P<0.05). VM was positively associated with EPO expression (r=0.284, P<0.05) but was not associated with EPO-R expression (P>0.05). CONCLUSION: These data suggest that increased EPO/EPO-R expression may play an important role in cervical carcinogenesis. EPO overexpression may promote VM formation in CSCC.