Circulating Prostate Tumor Cells Detected By Reverse Transcription-PCR In Men With Localized Or Castration-Refractory Prostate Cancer

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology
Article Date: 31 Mar 2009 - 3:00 PDT

email to a friend   printer friendly   opinions  

UroToday.com - In the journal Clinical Chemistry, Dr. Pauliina Helo and the group of Dr. Hans Lilja at Memorial Sloan-Kettering Cancer Center measured circulating tumor cells (CTCs) in prostate cancer patients by the commercially available CellSearch;Veridex assay and compared it to a RT-PCR methodology from their laboratory. As background, CTCs are under intense investigation as a new and more sensitive marker of disease progression in cancer patients. The CellSearch assay uses semiautomated immuomagnetic capture and detection of intact CTCs. The hypothesis is that RT-PCT of tissue-specific transcripts may be more sensitive.

The investigators developed standardized and reproducible RT-PCR assays for PSA and the human kallikrein 2 (KLK2) mRNAs. The assay was tested on 76 patients with castration-resistant prostate cancer (CRPC) and three groups of patients with localized disease; group 1 was 42 patients who had undergone radical prostatectomy (RP) at MSKCC within 6 months of sample collection, group 2 was 87 patients pre-RP for clinically localized CaP whose pathology revealed at least one unfavorable feature, and group 3 was 51 patients from the University Hospital Hamburg who were to undergo either RP or radiotherapy. The relationship between KLK mRNA and CellSearch STC results were analyzed in two ways; the proportion of patients categorized as either both positive or both negative in KLK mRNA and Cell Search assays, and second, the KLK mRNA and CTC results as continuous variables with correlation estimated by the Kendall . The association of the test to clinical outcomes was also assessed.

PSA mRNA and KLK2 mRNA were positive in 36% and 42% of CRPC patients, respectively (one or both positive in 49%) and negative in all healthy volunteers. CellSearch was positive in 48% of CRPC patients. The investigators also tested prostate stem cell antigen (PSCA) mRNA and it was positive in only 10% of CRPC patients. The status for either PSA or KLK2 mRNA was concordant with CellSearch counts in 82% of the CRPC patients. Among 34 patients with a negative CellSearch result (<5 CTCs), 7 had detectable PSA or KLK mRNA. The sensitivity of both PSA and KLK2 mRNA was 74%, that of either was 84%. Positive PSA or KLK2 mRNA status was found in 50% of patients with bone metastasis alone, but no patients with soft tissue metastasis alone, while a positive CellSearch result was more frequent in patients with bone metastasis. The frequency of either a positive RT-PCR CellSearch assay was greater in patients who received chemotherapy vs. hormone deprivation alone. One or both mRNAs were detected in only 14% of group 1 and 7% of group 2 patients, demonstrating no association with unfavorable disease characteristics.

Helo P, Cronin AM, Danila DC, Wenske S, Gonzalez-Espinoza R, Anand A, Koscuiszka M, Väänänen RM, Pettersson K, Chun FK, Steuber T, Huland H, Guillonneau BD, Eastham JA, Scardino PT, Fleisher M, Scher HI, Lilja H

Clin Chem. 2009 Feb 20. Epub ahead of print
doi:10.1373/clinchem.2008.117952

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to: www.urotoday.com

Copyright © 2009 - UroToday

• Additional
• References
• Citations