The Use of Real-Time Reverse Transcription-PCR for Prostate-Specific Antigen mRNA to Discriminate between Blood Samples from Healthy Volunteers and from Patients with Metastatic Prostate Cancer

• Published in: Clinical cancer research Vol. 10; no. 22; pp. 7511 - 7519
• Main Authors: Patel, Kinnari, Whelan, Peter J., Prescott, Stephen, Brownhill, Samantha C., Johnston, Colin F., Selby, Peter J., Burchill, Susan A.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.11.2004
• Subjects: Antineoplastic agents; beta 2-Microglobulin - metabolism; Biological and medical sciences; Cell Line, Tumor; DNA, Complementary - metabolism; Gynecology. Andrology. Obstetrics; Humans; Leukocytes, Mononuclear - cytology; Male; Male genital diseases; Medical sciences; Neoplasm Metastasis; Nephrology. Urinary tract diseases; Neutrophils - cytology; Pharmacology. Drug treatments; Polymerase Chain Reaction; Prostate-Specific Antigen - biosynthesis; Prostatic Neoplasms - blood; Prostatic Neoplasms - diagnosis; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - metabolism; Sensitivity and Specificity; Time Factors; Transcription, Genetic; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Human; Biological fluid; Urinary system disease; Prostate disease; Healthy subject; Tumoral marker; Malignant tumor; Metastasis; Real time; Blood; Prostate specific antigen; Messenger RNA; Advanced stage; Male genital diseases; Reverse transcription polymerase chain reaction; Prostate cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-0166

Purpose: A clinical role for nonquantitative reverse transcription-PCR (RT-PCR) using prostate-specific antigen in blood samples from patients with prostate cancer remains undefined. Assay variation and detection of prostate-specific antigen mRNA illegitimate transcription may explain inconsistent results between studies. Defining levels of prostate-specific antigen mRNA expression in blood samples from healthy volunteers and patients with prostate cancer would allow cutoffs to be established to distinguish the two groups. Experimental Design: Quantitative real-time RT-PCR for prostate-specific antigen mRNA was established and levels of prostate-specific antigen mRNA measured in bloods samples from healthy volunteers ( n = 21) and patients with localized ( n = 27) and metastatic ( n = 40) prostate cancer. Results: Levels of prostate-specific antigen mRNA were significantly higher in blood samples from patients with metastatic prostate cancer than in blood samples from patients with localized prostate cancer ( P < 0.001) or in blood samples from healthy volunteers ( P < 0.01); levels between patients with localized prostate cancer and healthy volunteers were no different. Assay sensitivity to detect patients with metastatic prostate cancer was 68% with specificity of 95%. In patients with newly diagnosed metastatic prostate cancer, monitoring response to hormonal therapy was possible with this assay. No correlation between levels of prostate-specific antigen mRNA and serum prostate-specific antigen protein levels was found, suggesting that prostate-specific antigen mRNA and serum prostate-specific antigen protein levels reflect different features of prostate cancer, i.e. , circulating tumor cells and total tumor bulk, respectively. Conclusions: Quantitative RT-PCR discriminates patients with metastatic prostate cancer from healthy volunteers and patients with localized prostate cancer but cannot discriminate patients with localized prostate cancer from healthy volunteers. A role for quantitative RT-PCR has been identified in the assessment and monitoring of patients with metastatic prostate cancer.