Circulating prostate tumor cells detected by reverse transcription-PCR in men with localized or castration-refractory prostate cancer: concordance with CellSearch assay and association with bone metastases and with survival.
BACKGROUND
Reverse transcription-PCR (RT-PCR) assays have been used for analysis of circulating tumor cells (CTCs), but their clinical value has yet to be established. We assessed men with localized prostate cancer or castration-refractory prostate cancer (CRPC) for CTCs via real-time RT-PCR assays for KLK3 [kallikrein-related peptidase 3; i.e., prostate-specific antigen (PSA)] and KLK2 mRNAs. We also assessed the association of CTCs with disease characteristics and survival.


METHODS
KLK3, KLK2, and PSCA (prostate stem cell antigen) mRNAs were measured by standardized, quantitative real-time RT-PCR assays in blood samples from 180 localized-disease patients, 76 metastatic CRPC patients, and 19 healthy volunteers. CRPC samples were also tested for CTCs by an immunomagnetic separation system (CellSearch; Veridex) approved for clinical use.


RESULTS
All healthy volunteers were negative for KLK mRNAs. Results of tests for KLK3 or KLK2 mRNAs were positive (> or =80 mRNAs/mL blood) in 37 patients (49%) with CRPC but in only 15 patients (8%) with localized cancer. RT-PCR and CellSearch CTC results were strongly concordant (80%-85%) and correlated (Kendall tau, 0.60-0.68). Among CRPC patients, KLK mRNAs and CellSearch CTCs were closely associated with clinical evidence of bone metastases and with survival but were only modestly correlated with serum PSA concentrations. PSCA mRNA was detected in only 7 CRPC patients (10%) and was associated with a positive KLK mRNA status.


CONCLUSIONS
Real-time RT-PCR assays of KLK mRNAs are highly concordant with CellSearch CTC results in patients with CRPC. KLK2/3-expressing CTCs are common in men with CRPC and bone metastases but are rare in patients with metastases diagnosed only in soft tissues and patients with localized cancer.
Helo
Pauliina
P
Departments of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center,New York, NY 10065, USA.
Cronin
Angel M
AM
Danila
Daniel C
DC
Wenske
Sven
S
Gonzalez-Espinoza
Rita
R
Anand
Aseem
A
Koscuiszka
Michael
M
Väänänen
Riina-Minna
RM
Pettersson
Kim
K
Chun
Felix K-H
FK
Steuber
Thomas
T
Huland
Hartwig
H
Guillonneau
Bertrand D
BD
Eastham
James A
JA
Scardino
Peter T
PT
Fleisher
Martin
M
Scher
Howard I
HI
Lilja
Hans
H
D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics* / Q000556:secondary; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000235:genetics; D008297:Male; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology*; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D015996:Survival Rate
D012333:RNA, Messenger; D007610:Kallikreins