Osteopontin as an Adjunct to CA125 in Detecting Recurrent Ovarian Cancer

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Abstract
Purpose: CA125 is currently the only tumor marker to have a validated role in the postoperative monitoring of ovarian cancer. Osteopontin (OPN) is a putative plasma biomarker that was recently identified using high-throughput cDNA microarray technology. The purpose of this study was to test the hypothesis that OPN is a clinically useful adjunct to CA125 in detecting recurrent ovarian cancer. Experimental Design: Thirty-eight ovarian cancer patients had a single pretreatment blood sample and 200 postoperative specimens were prospectively collected during chemotherapy and follow-up. OPN measurements were performed using an enzyme-linked immunoassay, and CA125 levels were concurrently obtained. Wilcoxon’s signed rank-sum test was used to perform paired comparisons between pretreatment and postoperative OPN and CA125 measurements. Longitudinal mixed effects polynomial models were used to determine whether OPN and CA125 levels correlated with the development of recurrent ovarian cancer. Results: The median pretreatment OPN level was 178 ng/ml (range, 12–3468) and the median CA125 measurement was 812 units/ml (range, 12–81,500). There was a trend for OPN levels to decline after treatment was initiated (P = 0.07), but decreasing CA125 measurements were more consistently observed (P = 0.0009). The quadratic functional trends of OPN and CA125 were each highly significant (P < 0.0001). Although inferior to CA125 in predicting clinical response to therapy, OPN rose earlier in 90% (95% confidence interval, 56–100%) of the patients developing recurrent disease (median lead time, 3 months). Conclusions: OPN may be a clinically useful adjunct to CA125 in detecting recurrent ovarian cancer.