S100A8, S100A9, and the S100A8/A9 complex in circulating blood are not associated with prostate cancer risk-A re-evaluation study

BACKGROUND: To evaluate the diagnostic performance of plasma S100A8, S100A9, and the S100A8/A9 complex as novel markers to discriminate between benign and malignant prostatic diseases as recently suggested for S100A9. METHODS: The study included 90 prostate cancer (PCa) patients (pN0M0, n = 50; pN1M0, n = 27; M1, n = 13), 50 controls without PCa, and six patients within 72 hr after radical prostatectomy for repeated measurements. The S100 proteins were analyzed with specific ELISAs. Comparisons were made to the prostate-specific antigen (tPSA) and the ratio of free to tPSA (%fPSA). RESULTS: The plasma concentrations of the S100 proteins in controls had either significantly higher values (S100A8; P = 0.020) or the tendency to higher values compared with the results in PCa patients. Differences between the three PCa groups were almost negligible. No correlation could be found between S100 protein levels and PSA concentration (r(s) = -0.110 to 0.433, P = 0.317-0.433) or prostate volume (r(s) = -0.038 to 0.018, P = 0.676-0.844). Tumor stage and tumor grade had no observed effect on S100 protein concentrations. After prostatectomy, there were discordant elimination kinetics for PSA and the S100 proteins, as the S100 proteins partially increased while PSA continuously decreased. Analyses of receiver-operating curves showed that, compared with PSA, S100A8, S100A9, and S100A8/A9 did not improve the differentiation between patients with and without PCa, while the discrimination ability was significantly lower than that of %fPSA. CONCLUSIONS: Our re-evaluation study showed that S100A8, S100A9, and the complex S100A8/A9 were less indicative than %fPSA and that they are not suitable to replace PSA.