Urokinase-plasminogen-activator receptor expression in disseminated tumour cells in the bone marrow and peripheral blood of patients with clinically localized prostate cancer.
OBJECTIVE To evaluate the expression of urokinase-plasminogen-activator receptor (uPA-R) in disseminated tumour cells (DTC) in bone marrow (BM) and peripheral blood (PB) of patients with clinically localized prostate cancer before radical prostatectomy (RP), and to assess the associations with pathological variables and prognosis. PATIENTS AND METHODS In all, 52 patients (47 with clinically localized cancer and five with benign prostatic hyperplasia, BPH, as controls) were prospectively enrolled. BM and PB samples were drawn before surgery. DTC were enriched using a commercial system, cytokeratin (CK) 8/18 was used to detect DTC, and uPA-R expression was detected by dual-immunostaining of the DTC. The final pathology of the RP specimen was compared with the results of immunostaining. Follow-up was initiated to detect tumour relapse (defined as a prostate-specific antigen (PSA) level of > or =0.2 ng/mL). RESULTS Overall, there was expression of 'CK + uPA-R' in 60% of the BM and in 19% of the PB specimens. Expression of this marker in BM was most significantly increased in those with unfavourable Gleason scores (P = 0.004), followed by high-risk cancer (P = 0.005). The relative risk for CK + uPA-R expression in the BM was 3.1 times higher in high-risk than in low-risk prostate cancer. No relevant expression rates were detected for PB. In the control group, no patient showed CK or uPA-R expression in BM or PB. The PSA-recurrence free survival was significantly lower in patients with CK + uPA-R-positive BM cells (P = 0.01). CONCLUSION In this pilot study, the preoperative detection rate of CK + uPAR expression in BM of patients with prostate cancer increased with Gleason score and in those with high-risk disease. All patients with a later PSA relapse had had uPA-R expression in their DTC from the BM. DTC with uPA-R expression was an adverse prognostic factor for prostate cancer.
Thomas
Christian
C
Department of Urology, Johannes-Gutenberg University, Mainz, Germany. thomas@urologie.klinik.uni-mainz.de
Wiesner
Christoph
C
Melchior
Sebastian W
SW
Schmidt
Folke
F
Gillitzer
Rolf
R
Thüroff
Joachim W
JW
Pfitzenmaier
Jesco
J
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D004812:Epidemiologic Methods; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000175:diagnosis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*
D014408:Biomarkers, Tumor; D055293:Receptors, Urokinase Plasminogen Activator; D017430:Prostate-Specific Antigen