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

被引:108
作者
Helo, Pauliina [2 ]
Cronin, Angel M. [2 ]
Danila, Daniel C. [3 ]
Wenske, Sven [2 ]
Gonzalez-Espinoza, Rita [1 ]
Anand, Aseern [1 ]
Koscuiszka, Michael [3 ]
Vaananen, Riina-Minna [4 ]
Pettersson, Kim [4 ]
Chun, Felix K. -H. [5 ]
Steuber, Thomas [5 ]
Huland, Hartwig [5 ]
Guillonneau, Bertrand D. [2 ]
Eastham, James A. [2 ]
Scardino, Peter T. [2 ]
Fleisher, Martin [1 ]
Scher, Howard I. [3 ]
Lilja, Hans [1 ,2 ,3 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Clin Labs, New York, NY 10065 USA
[2] Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10065 USA
[3] Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10065 USA
[4] Univ Turku, Dept Biotechnol, Turku, Finland
[5] Univ Hamburg Hosp, Dept Urol, D-2000 Hamburg, Germany
关键词
POLYMERASE-CHAIN-REACTION; HUMAN GLANDULAR KALLIKREIN; PERIPHERAL-BLOOD; BREAST-CANCER; RT-PCR; RADICAL PROSTATECTOMY; MESSENGER-RNAS; FOLLOW-UP; ANTIGEN; QUANTIFICATION;
D O I
10.1373/clinchem.2008.117952
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
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 (TM); Veridex) approved for clinical use. RESULTS: All healthy volunteers were negative for KLK mRNAs. Results of tests for KLK3 or KLK2 mRNAs were positive (>= 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 T, 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. (C) 2009 American Association for Clinical Chemistry
引用
收藏
页码:765 / 773
页数:9
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