Overexpression of fibulin-4 is associated with tumor progression and poor prognosis in patients with cervical carcinoma.

Fibulin-4, a member of the fibulin family of extracellular glycoproteins, is implicated in the progression of a number of types of cancer. However, the function of fibulin-4 in cervical cancer progression remains unexplored. Fibulin-4 mRNA and protein expression levels in normal cervical tissue, cervical intraepithelial neoplasia (CIN), cervical carcinoma, highly invasive subclones and low-invasive subclones were evaluated by real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. Serum fibulin-4 levels in patients with CIN and cervical carcinoma were measured by enzyme-linked immunosorbent assay. To assess the angiogenic properties of fibulin-4, vascular endothelial growth factor (VEGF) expression and tumor microvessel density (MVD) were analyzed in the cervical carcinoma cases by immunohistochemistry. Fibulin-4 expression was upregulated in the cervical carcinoma cases, and was positively correlated with MVD and VEGF expression. Fibulin-4 overexpression and high serum levels were significantly associated with advanced stage, low differentiation, lymph node metastasis, and poor prognosis in patients with cervical cancer. Fibulin-4 expression was also found to be overexpressed in highly invasive subclones when compared with the low-invasive subclones. Fibulin-4 is a newly identified glycoprotein that is overexpressed in cervical carcinoma. Fibulin-4 promotes angiogenesis and is associated with poor prognostic clinicopathologic features. This study demonstrated that fibulin-4 may serve as a new prognostic factor and as a potential therapeutic target for patients with cervical carcinoma.