Annexin A3 In Urine: A Highly Specific Noninvasive Marker For Prostate Cancer Early Detection

A group of European investigators reported in the online edition of the Journal of Urology that Annexin A3 (ANXA3) combined with PSA improves the detection of prostate cancer (CaP). ANXA3 is a calcium and phospholipid binding protein involved in cell migration, differentiation, immunomodulation and bone metabolism. ANXA3 is implicated in CaP tumorigenesis. The researchers hypothesized that measurement of ANXA3 and PSA would outperform PSA alone in the detection of CaP.

The study cohort included 591 patients at 4 European urology clinics. ANXA3 was measured in urine collected after 20 seconds of digital prostate massage by Western blotting. Serum PSA and it derivatives were also measured. A mathematical function combining ANXA3/total PSA (ANXA3/tPSA) was developed. A training set derived from 243 patients in whom biopsy and initial PSA results were known was analyzed using logistic regression and optimized for 3 subpopulations; patients in the PSA ranges 2-6ng/ml, 4-10ng/ml and the entire training population. The optimized parameters from the training data were evaluated in a second validation set of 264 men.

CaP was detected by 10-core prostate biopsy in 368 of 591 men, and 223 men were found not to have CaP. The model was then run for the 3 subpopulations using the following variables; initial tPSA, density normalized ANXA3 (s.anx.d), combinations of s.anx.d and PSA related variables, and results of the entire dataset with nonlinear combinations of variables. In men with a tPSA 2-6ng/ml, ANXA3 readout had an area under the ROC curve (AUROC) of 0.725 compared to 0.679 or less for all PSA-related readouts. A combined variable of s.anx.d/tPSA was superior to all others with an AUROC of 0.812. The best AUROC obtained was 0.832 attained by a nonlinear combination of s.anx.d and percent fPSA in 280 men with a tPSA between 4-10ng/ml. Correlation analysis of tPSA and ANXA3 values revealed that the 2 markers are independent. These data suggest that ANXA3 complements PSA in the detection of CaP.

Schostak M, Schwall GP, Poznanovic? S, Groebe K, Müller M, Messinger D, Miller K, Krause H, Pelzer A, Horninger W, Klocker H, Hennenlotter J, Feyerabend S, Stenzl A, Schrattenholz A
J Urol. 2009 Jan;181(1):343-53
doi:10.1016/j.juro.2008.08.119