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Detection of α-Methylacyl-Coenzyme-A Racemase Transcripts in Blood and Urine Samples of Prostate Cancer Patients

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Abstract

Background: α-Methylacyl-coenzyme-A racemase (AMACR) has been shown to be a highly specific marker for prostate cancer cells, even in the earliest stages of malignant progression. It is expressed at much higher levels than prostate-specific antigen (PSA) in malignant tissues, and is not expressed at appreciable levels in normal prostatic epithelium. In this study, we demonstrate the quantitative detection of AMACR transcripts in peripheral blood of prostate cancer patients using real-time RT-PCR. In addition, we have undertaken a pilot study to demonstrate the potential application of this technique for the detection of prostate tumor cells in urine samples from patients with prostate cancer.

Methods: A real-time RT-PCR assay was developed for detection of the expression of AMACR in prostate cancer patients. Blood samples from 163 patients were tested at various stages of disease progression, with or without therapy. Blood specimens from patients with benign prostate disorders and other types of cancer were also evaluated.

Results: In 28 of 58 samples from patients with known metastatic disease who were undergoing treatment, an AMACR expression signal above the cut-off value was detected, consistent with the presence of circulating tumor cells. In 39 of 88 patients with presumptive organ-confined disease, there was evidence of low levels of circulating tumor cells. Comparison of AMACR RT-PCR with known serum PSA values indicated that a combination of these parameters significantly increased the sensitivity for detection of progressive disease. In a pilot study analyzing urine samples from seven prostate cancer patients, elevated AMACR expression levels were detected in the urine sediments of four of six stage-T1 prostate cancer patients and in the one patient with stage-T2 prostate cancer.

Conclusion: The data presented in this study indicates that AMACR real-time RT-PCR may aid in the detection and staging of prostate cancer.

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Acknowledgments

We would like to thank Drs Mark Kiviat, Gary Goodman, Richard Osten-son, and Steve Loop for providing blood samples from prostate cancer patients and individuals with other urological disorders. We would also like to thank Andrew Lin for his assistance in facilitating sample and data transfer. This work was supported in part by grant R44 CA-80518 from the National Cancer Institute. The authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Hematologics Inc., 113 First Avenue North, Seattle, Washington, 98109, USA

    Barbara K. Zehentner

  2. GSK-Bio, Seattle, Washington, USA

    Heather Secrist, XinQun Zhang & Dawn C. Hayes

  3. Good Samaritan Hospital, Puyallup, Washington, USA

    Richard Ostenson

  4. Swedish Hospital, Seattle, Washington, USA

    Gary Goodman

  5. Amgen Inc., Seattle, Washington, USA

    Jiangchun Xu

  6. Harborview Medical Center, Seattle, Washington, USA

    Mark Kiviat & Nancy Kiviat

  7. Cepheid, Sunnyvale, California, USA

    David H. Persing

  8. Inbios International Inc., Seattle, Washington, USA

    Raymond L. Houghton

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  1. Barbara K. Zehentner
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Correspondence to Barbara K. Zehentner.

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Zehentner, B. ., Secrist, H., Zhang, X. et al. Detection of α-Methylacyl-Coenzyme-A Racemase Transcripts in Blood and Urine Samples of Prostate Cancer Patients. Mol Diag Ther 10, 397–403 (2006). https://doi.org/10.1007/BF03256217

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