Association of circulating tumor cells with tumor-related methylated DNA in patients with hormone-refractory prostate cancer.

OBJECTIVES

To assess whether circulating tumor cells with tumor-related methylated DNA can be used to predict survival in patients with hormone-refractory prostate cancer.

METHODS

Blood samples from 76 patients with hormone-refractory prostate cancer were analyzed. Circulating tumor cells were enumerated with the CellSearch System in whole blood. This system was developed using an epithelial cell adhesion molecule antibody-based immunomagnetic capture and automated staining methodology. Hypermethylation at adenomatosis polyposis coli, glutathione-S-transferase-pi, prostaglandin-endoperoxide synthase 2, multidrug resistance 1 and Ras association domain family 1 isoform A was analyzed using a sensitive SYBR green methylation-specific polymerase chain reaction. Patient charts were retrospectively examined.

RESULTS

Median overall survival time was 19.3 months (range 11-48). Of the 76 patients, 47 (62%) had five or more circulating tumor cells, with a median overall survival of 12.0 months compared with 26.0 months for patients with fewer than five circulating tumor cells (P < 0.001). Circulating tumor cells were detected in 36 of 39 (92%) patients with tumor-related methylated DNA but only 11 of 37 (30%) patients without methylated DNA (P < 0.001). Thirty-nine (51%) patients had one or more methylated marker. Their median overall survival time was 12.0 months compared with 48.0 months or more for patients without methylated DNA (P < 0.001). Prostate-specific antigen-doubling time, circulating tumor cells and methylated DNA were independent predictors of overall survival time.

CONCLUSIONS

Hormone refractory prostate cancer patients with circulating tumor cells and/or tumor-related methylated DNA show a significantly poorer outcome than those without these blood markers.