Elsevier

Urology

Volume 60, Issue 2, August 2002, Pages 270-275
Urology

Adult urology
Increased expression of PSA mRNA during brachytherapy in peripheral blood of patients with prostate cancer

This work was presented at the 48th Annual Meeting of the Radiation Research Society, April 2001, San Juan, Puerto Rico.
https://doi.org/10.1016/S0090-4295(02)01703-XGet rights and content

Abstract

Objectives. To determine the extent of iatrogenic tumor cell dissemination during brachytherapy by assessing prostate-specific antigen (PSA) mRNA expression in circulating prostate tumor cells using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The instrumentation used in the radioisotope seed placement of the prostate causes trauma to blood vessels and provides a vascular access for tumor cells that can lead to potential iatrogenic dissemination and systemic failure.

Methods. Twenty-five patients treated for brachytherapy were recruited in the study. Controls included 4 normal men and 1 woman; case controls included 4 patients who underwent prostate biopsy for prostate cancer diagnosis. Peripheral blood (10 mL) was collected before, during, and after the brachytherapy procedure. Total RNA was isolated from mononuclear cells and phosphorus-32 RT-PCR was performed to analyze the mRNA expression of PSA and G6PDH genes.

Results. Of 25 patients, 23 were negative for PSA mRNA expression and 2 were positive for PSA mRNA expression before brachytherapy. Of the 23 patients who were negative for PSA mRNA expression before treatment, 15 patients (65%) turned positive during or after brachytherapy and the remaining 8 patients remained negative throughout the treatment. Eight of the 25 patients developed rising serum PSA levels. Of these 8 patients, 1 (12.5%) did not have PSA mRNA expression in the peripheral blood before, during, or after brachytherapy; the remaining 7 patients who developed rising serum PSA levels had PSA mRNA expression after brachytherapy (P = 0.03).

Conclusions. These findings strongly suggest that iatrogenic shedding of prostate cells occurs as a result of brachytherapy and raises the concern that these cells liberated at the time of brachytherapy increase the risk of metastatic deposits and results in systemic failure, as measured by serum PSA levels.

Section snippets

Patients

Twenty-five patients undergoing brachytherapy for prostate cancer were recruited for this study with informed consent approved by University of Kentucky Institutional Review Board. Four patients undergoing prostate biopsy who were negative for cancer were used as case controls to determine the iatrogenic effect of the instrumentation on the normal prostate on the PSA mRNA levels. Peripheral blood samples from 4 normal men and 1 woman were used as negative controls. Patients were followed up by

Sensitivity of PSA RNA detection by 32P-RT-PCR

A semiquantitative 32P-RT-PCR was used to analyze the sensitivity of PSA mRNA detection in total PSA-negative normal female RNA contaminated with the RNA from PSA-positive LNCaP control cells. By this assay, the presence of PSA mRNA expression was detected in as low as 10−7 μg LNCaP RNA in 1 μg of normal female RNA (Fig. 1A). This contamination simulates one tumor cell in 105 mononuclear cells. The PSA/G6PDH densitometry values were directly proportional to the level of contamination by LNCaP

Comment

Radical prostatectomy, brachytherapy, and external beam radiotherapy are currently used for the treatment of localized disease; however, the wide spectrum of biologic behavior exhibited by prostatic neoplasms poses a difficult problem in predicting the clinical course for an individual patient.15 Traditional prognostic markers, such as grade, clinical stage, and pretreatment serum PSA, are used extensively and are of some prognostic value for individual men.16, 17 The pattern of post-treatment

Conclusions

Our results suggest for the first time in published reports that a substantial number of patients undergoing brachytherapy have iatrogenic dissemination of prostate cancer cells in the peripheral blood caused by the insertion of needles in the prostate gland. Also, the detection of PSA mRNA in the peripheral circulation appears to have a significant correlation with biochemical failure after interstitial brachytherapy and needs additional study in a larger patient population.

References (27)

Cited by (8)

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    The amount of circulating nucleic acids however cannot be justified by the number of cancer cells existing in serum [9], leading to the hypothesis that tumor specific circulating or cell-free nucleic acids come from the necrosis [19,20] or apoptosis [24,25] of cancer cells or they are even actively released by them in microvesicles [26,27,29]. Circulating RNA has been isolated from the plasma or serum of patients suffering from various types of malignancies such as breast cancer [49–56], lung cancer [57–63], prostate cancer [64–78], thyroid cancer [79–98], hepatocellular carcinoma [5,72,75,99–112], melanoma [113–116], gastric cancer [117], renal cell cancer [118], oesophageal cancer [119,120], rectal carcinoma [121], gynecologic malignancies [122], pancreatic cancer [61], colon cancer [61], bladder cancer [16] and solid tumors [123], and has been used as a biological marker either for the early detection and diagnosis of the disease [64,100], or as a marker of recurrence patterns [81,121], survival predictor [51], follow up and surveillance marker [79,82]. In particular, in breast cancer, measurement of serum metastasin mRNA has been proposed as a screening tool, predicting poor survival and distant metastases [51], whereas measurement of circulating 5T4 mRNA as having the potential to identify patients who could benefit from a 5T4-targeted therapy [53].

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Ayisha Siddiqua was the recipient of the student travel award for this study from the Radiation Research Society.

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