Clinical significance of osteopontin expression in cervical cancer

Abstract

New diagnostic markers, other than squamous cell carcinoma (SCC) antigen, are needed for the detection of cervical cancer. Osteopontin (OPN) is a candidate frequently associated with several human malignancies. The purpose of this study was to evaluate the clinical significance of OPN expression as a diagnostic and prognostic biomarker for cervical cancer. Immunohistochemical staining of tissue from 97 cervical cancer cases and 22 healthy subjects was performed in order to determine the source of elevated plasma OPN levels. In addition, plasma OPN levels of 81 patients with cervical cancer, 34 patients with carcinoma in situ (CIS) of the uterine cervix, and those of 283 healthy women were measured with a commercially available solid-phase sandwich enzyme-linked immunosorbent assay (ELISA). The correlation between OPN levels and clinical features were examined and compared to SCC antigen levels in the cervical cancer cases. Immunohistochemical staining revealed OPN immunoreactivity in 67.0% (65/97) of cervical cancer tissues, and the immunostaining score in the cervical cancer tissue sections was 2.06 (95% CI, 1.70-2.42). There was no significant difference in immunostaining scores based on age, tumor size, and tumor stage, but higher scores (3.0< score <or=6.0) were significantly correlated with overall survival (P = 0.002) and disease-free survival (P = 0.033). Plasma OPN levels in women with cervical cancer (mean 355.8 ng/ml) were significantly higher (P < 0.001) than those of women with CIS (mean: 185 ng/ml) and healthy controls (mean 100 ng/ml). Within the cervical cancer patients, OPN levels correlated with increasing tumor size (P = 0.008) and tumor stage (P < 0.001). The sensitivity and specificity of OPN in detecting cervical cancer was 50.6 and 95.0%, respectively (cutoff value 215.5 ng/ml). Using a combination of markers proved to bring more sensitive results than using one marker (sensitivity: 65.4%, specificity: 90.9%). High plasma OPN levels (>215.5 ng/ml) were also correlated with disease-free survival (P = 0.038). These results suggest that plasma OPN levels are potentially useful as a diagnostic and prognostic biomarker for cervical cancer.