Circulating Prostate Cells Research Articles

Detection of circulating prostate carcinoma cells via an enhanced reverse transcriptase-polymerase chain reaction assay in patients with early stage prostate carcinoma. Independence from other pretreatment characteristics.

Circulating prostate cells can be detected in the venous blood of patients with clinically localized prostate carcinoma by applying reverse transcriptase-polymerase chain reaction (RT-PCR) techniques using primers specific for the prostate specific antigen (PSA) gene. This study evaluates whether the detection of circulating cells correlates with established prognostic factors, treatment, and pathologic stage. Two hundred and twenty-seven patients with clinically localized adenocarcinoma of the prostate had an RT-PCR assay performed as part of their staging evaluation. No treatment decisions were made on the basis of the RT-PCR results. Of these, 156 patients were treated with radical prostatectomy (RP) and 71 with radical external beam radiotherapy (EBRT). Forty-eight patients were treated with hormonal therapy prior to RP (n = 39) or EBRT (n = 9). The prognostic factors analyzed for their relationship to RT-PCR were clinical stage, pretreatment serum PSA levels, Gleason score of the biopsy specimen, and Gleason score of the surgical specimen. An analysis of the relationship between treatment and RT-PCR results was also performed. Multivariate logistic regression analysis of predictors of RT-PCR positivity was performed as well. In addition, univariate and multivariate analyses of predictors of pathologic stage, including RT-PCR, were performed. Sixty-one patients (26.9%) had a positive RT-PCR assay. There was no relationship between clinical stage, pretreatment PSA, biopsy Gleason score, or surgical Gleason score and RT-PCR positivity. In univariate analysis, patients treated with RP had a higher rate of RT-PCR positivity than patients treated with EBRT (P = 0.054). However, in multivariate logistic regression analysis no factor, including treatment with RP, was a significant predictor of RT-PCR positivity. RT-PCR and pretreatment PSA predicted pathologic stage in univariate and multivariate analyses (P < 0.0001 and P = 0.002, respectively). The detection of circulating prostate cells using RT-PCR occurs in approximately 25% of early stage prostate carcinoma patients and is independent of other established prognostic factors. In addition, a positive RT-PCR assay is a strong predictor of pathologic upstaging in patients with clinically organ-confined disease.

Value of the Preoperative Detection of Prostate-Specific-Antigen-Positive Circulating Cells by Nested RT-PCR in Patients Submitted to Radical Prostatectomy

To assess the value of the detection of circulating prostate cells [prostate-specific antigen (PSA) positive] by reverse-transcriptase nested polymerase chain reaction (nested RT-PCR) to improve the staging of clinically localized prostate cancer. Nested PCR was performed on blood samples of 29 patients submitted to radical prostatectomy for clinically localized (T1-T2) prostate cancer. Nine patients with various benign urologic diseases comprised the negative control group. Incubation was for 25 cycles for each PCR, using beta 2-microglobulin to test the integrity of RNA samples. Each sample was tested in quadruplicate and analyzed by agarose gel electrophoresis, blotted and hybridized with specific internal primers. Nested PCR results were compared with the pT stage of the prostate specimen, processed according to the Stanford method. In 6 out of 29 patients (20.7%) with clinically localized prostate cancer, circulating prostate cells were detected by nested PCR. There was no relationship between pathologic stage and RT-PCR results. Eleven out of 14 pT2 patients (78.6%) were PCR negative and only 3 out of 15 pT3 patients (20%) were PCR positive. All control samples were PCR negative. In selected patients with T1-T2 prostate cancer, there was no relationship between pathologic stage and the presence of circulating PSA-positive cells detected by nested PCR. However, in 20.7% of patients with clinically localized prostate cancer, circulating prostate cancer cells were detected. A further follow-up based on PSA is necessary to clarify the clinical relevance of this biologic anomaly.

The use of RT-PCR for prostate-specific antigen assay to predict potential surgical failures before radical prostatectomy: molecular staging of prostate cancer.

To assess the potential role of a recently developed reverse transcriptase-polymerase chain reaction (RT-PCR) assay for prostate-specific antigen (PSA), that detects circulating prostate cells in patients with prostate cancer, in the management of clinically localized cancer. A total of 138 men (mean age 62.5 years, range 49-70) scheduled for radical retropubic prostatectomy had an RT-PCR assay before surgery. The results were compared with the final pathological stage of disease, the results from local imaging techniques, serum PSA levels, digital rectal examination (DRE) and Gleason score. Enhanced RT-PCR for PSA was the best predictor of potential surgical failures; 70% of patients with positive surgical margins or invasion into the seminal vesicle were identified pre-operatively by a positive RT-PCR assay (odds ratio = 12.0, positive predictive value = 64%, negative predictive value = 87%). RT-PCR was able to identify pre-operatively patients with adverse pathology, despite low serum PSA values (< 4.0 ng/mL). In patients with high PSA level (> 10 ng/mL), RT-PCR discriminated between potentially curable candidates and those with established extraprostatic disease. RT-PCR for PSA adds unique prognostic information when considering patients for radical surgery. The final role for the RT-PCR assay is as yet undefined; however, the ability to detect potential surgical failures pre-operatively using a molecular approach should have a significant impact on the management of patients with prostate cancer.

Enhanced detection of hematogenous circulating prostatic cells in patients with prostate adenocarcinoma by using nested reverse transcription polymerase chain reaction assay based on prostate-specific membrane antigen

We report the development of a new sensitive nested reverse transcription-polymerase chain reaction (RT-PCR) assay, using primers derived from the prostate-specific membrane antigen (PSM) cDNA sequence, to detect an hematogenous spread of prostate adenocarcinoma cells. In 60 patients with a biopsy-proven prostate cancer, PSM and PSA RT-PCR detected circulating prostate cells in 40 and 20 patients, respectively. In pT4 M+ and pT3 M+ disease patients, nested PSM primers detected cells in 28 of 33 patients (85%), whereas nested PSA primers detected cells in 17 of 33 (51%). In patients with organ-confined cancer spread (pT2a and pT2b patients) before radical prostatectomy, nested PSM RT-PCR detected circulating prostatic epithelial cells in 6 of 17 patients (35%), which suggests that an hematogenous spread of prostate cells may occur early in prostate cancer history. Altogether, these results suggest that the detection of PSM-expressing cells in blood may predict the development of cancer in patients without clinically apparent prostate cancer. Nevertheless, the potential application and the clinical significance of detection of hematogenous prostate cells through the use of nested PSM primers need an extensive longitudinal study.