Showing papers on "Prostate published in 1995"

Prostate cancer in a transgenic mouse.

Abstract: Progress toward understanding the biology of prostate cancer has been slow due to the few animal research models available to study the spectrum of this uniquely human disease. To develop an animal model for prostate cancer, several lines of transgenic mice were generated by using the prostate-specific rat probasin promoter to derive expression of the simian virus 40 large tumor antigen-coding region. Mice expressing high levels of the transgene display progressive forms of prostatic disease that histologically resemble human prostate cancer, ranging from mild intraepithelial hyperplasia to large multinodular malignant neoplasia. Prostate tumors have been detected specifically in the prostate as early as 10 weeks of age. Immunohistochemical analysis of tumor tissue has demonstrated that dorsolateral prostate-specific secretory proteins were confined to well-differentiated ductal epithelial cells adjacent to, or within, the poorly differentiated tumor mass. Prostate tumors in the mice also display elevated levels of nuclear p53 and a decreased heterogeneous pattern of androgen-receptor expression, as observed in advanced human prostate cancer. The establishment of breeding lines of transgenic mice that reproducibly develop prostate cancer provides an animal model system to study the molecular basis of transformation of normal prostatic cells and the factors influencing the progression to metastatic prostate cancer.

Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer.

Abstract: Background Metastatic prostate cancer is a leading cause of cancer-related death in men. The rate of response to androgen ablation is high, but most patients relapse as a result of the outgrowth of androgen-independent tumor cells. The androgen receptor, which binds testosterone and stimulates the transcription of androgen-responsive genes, regulates the growth of prostate cells. We analyzed the androgen-receptor genes from samples of metastatic androgen-independent prostate cancers to determine whether mutations in the gene have a role in androgen independence. Methods Complementary DNA was synthesized from metastatic prostate cancers in 10 patients with androgen-independent prostate cancer, and the expression of the androgen-receptor gene was estimated by amplification with the polymerase chain reaction. Exons B through H of the gene were cloned, and mutations were identified by DNA sequencing. The functional effects of the mutations were assessed in cells transfected with mutant genes. Results All andr...

The Role of Increasing Detection in the Rising Incidence of Prostate Cancer

Abstract: Objective. —To assess the reasons for the dramatic surge in prostate cancer incidence from 1986 to 1991. Design. —Population-based study of incidence rates and procedures used to detect and diagnose prostate cancer derived from Medicare claims data and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program from 1986 to 1991. Setting. —Four SEER areas (Connecticut; Atlanta, Ga; Detroit, Mich; and Seattle—Puget Sound, Wash) covering approximately 6% of the US population. Participants. —A 5% random sample of male fee-for-service Medicare beneficiaries aged 65 years and older without cancer, and all men with prostate cancer diagnosed at 65 years of age and older residing in the four areas. Main Outcome Measures. —The age-adjusted rates of prostate cancer incidence, prostate needle biopsy, transurethral resection of the prostate, serum prostate-specific antigen (PSA) testing, and transrectal ultrasound. Results. —The age-adjusted incidence rate of prostate cancer among men aged 65 years and older in the four SEER areas rose 82% from 1986 to 1991, with the largest annual increases occurring in 1990 (20%) and 1991 (19%). Prostate needle biopsy rates increased while the use of transurethral resection of the prostate declined from 1986 to 1991. The rising needle biopsy rate has been driven by an exponential increase in PSA testing in the general population from 1988 to 1991 and, to a much lesser extent, the increasing use of transrectal ultrasound since 1986. The use of PSA or transrectal ultrasound has increased across age and race groups and in different geographic areas. However, there remain wide geographic variations in the use of PSA screening. Conclusions. —The recent dramatic epidemic of prostate cancer is likely the result of the increasing detection of tumors resulting from increased PSA screening. The magnitude and rapidity of the incidence rise suggest that changes in the intensity of medical surveillance is the most plausible explanation for this trend. Implications. —The rapid diffusion of screening interventions that have the ability to detect latent asymptomatic disease leads to important concerns regarding costs and patient quality of life for men aged 65 years and older. Geographic variability in the adoption of PSA testing underscores uncertainty and disagreement about its value for reducing prostate cancer mortality. More research is required to determine the effectiveness of screening for prostate cancer. (JAMA. 1995;273:548-552)

Evaluation of percentage of free serum prostate-specific antigen to improve specificity of prostate cancer screening.

Abstract: Objective. —To evaluate measurement of percentage of free prostate-specific antigen (PSA) in serum to improve the specificity of prostate cancer screening in men with serum PSA levels between 4.1 and 10.0 ng/mL. Design. —Retrospective, nonrandomized analysis using a research assay for measuring free PSA in frozen serum from men with a spectrum of prostate sizes and digital rectal examination results. Setting. —General community outpatient prostate cancer screening program at a university center. Patients. —One hundred thirteen men aged 50 years or older, 99% of whom were white, with serum PSA concentrations of 4.1 to 10.0 ng/mL, including 63 men with histologically confirmed benign prostatic hyperplasia, 30 with prostate cancer with an enlarged gland, and 20 with cancer with a normal-sized gland. All study volunteers had undergone prostatic ultrasonography and biopsy. Main Outcome Measures. —Percentage of free PSA in serum and percentage of free PSA cutoff that maintained at least 90% sensitivity for prostate cancer detection. Results. —Median percentage of free PSA was 9.2% in men with cancer and a normal-sized gland, 15.9% in men with cancer and an enlarged gland, and 18.8% in men with benign prostatic hyperplasia ( P Conclusions. —Measurement of percentage of free serum PSA improves specificity of prostate cancer screening in selected men with elevated total serum PSA levels and can reduce unnecessary prostate biopsies with minimal effects on the cancer detection rate; however, further studies are needed to define optimal cutoffs. Final evaluation of PSA screening also must consider the ability of current treatments to improve the prognosis of screen-detected prostate cancer. ( JAMA . 1995;274:1214-1220)

Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate.

Abstract: Prostate cancer is the second most common cause of death from cancer in U.S. men, and advanced, hormone-refractory disease is characterized by painful osteoblastic bone metastases. Endothelin-1, more commonly known as a potent vasoconstrictor, is a normal ejaculate protein that also stimulates osteoblasts. We show here that plasma immunoreactive endothelin concentrations are significantly elevated in men with metastatic prostate cancer and that every human prostate cancer cell line tested produces endothelin-1 messenger RNA and secretes immunoreactive endothelin. Exogenous endothelin-1 is a prostate cancer mitogen in vitro and increases alkaline phosphatase activity in new bone formation, indicating that ectopic endothelin-1 may be a mediator of the osteoblastic response of bone to metastatic prostate cancer.

Overexpression of bcl-2 Protects Prostate Cancer Cells from Apoptosis in Vitro and Confers Resistance to Androgen Depletion in Vivo

Abstract: Normal (nonneoplastic) human prostatic secretory epithelial cells do not express the bcl-2 protein. However, a recent immunohistochemical survey of neoplastic human prostate tissues showed that a fraction of primary untreated prostate adenocarcinoma cells expressed this apoptosis-suppressing oncoprotein at significant levels (Colombel et al., Am. J. Pathol., 143: 390-400, 1993). Additionally, a number of hormone-refractory prostatic adenocarcinomas obtained from hormonally-treated patients (subsequent to surgical or drug castration therapy) were examined and were found to be uniform in their elevated expression of bcl-2 oncoprotein. The results of this preliminary survey imply that bcl-2 expression distinguishes a subgroup of primary human prostate cancers and that the expression of this protein might be a factor enabling prostate cancer cells to survive in an androgen-deprived environment. The current study was undertaken to determine the degree to which overexpression of bcl-2 can protect human prostate cancer cells from apoptotic stimuli in vitro and in vivo. Human prostate cancer cells (LNCaP) were transfected with a neomycin-selectable eucaryotic expression vector containing cDNA encoding human bcl-2. Transfected clonal variants that express bcl-2 protein (LNCaP/bcl-2) were unaltered with regard to their basal growth rate in 10% serum-containing medium, or with regard to their expression of the differentiated human prostate cell gene products prostate-specific antigen or androgen receptor protein. The bcl-2-transfected clones were altered, however, with regard to their growth rate in charcoal-stripped serum lacking dihydrotestosterone. Additionally, in contrast to the parental or control-transfected cell lines, LNCaP/bcl-2 cells were highly resistant to a variety of apoptotic stimuli in vitro including serum starvation and 10 nM phorbol ester (phorbol 12-myristate 13-acetate) supplementation of the medium. Lastly, the overexpression of bcl-2 by these prostate cancer cells altered their tumorigenic potential in a nude mouse assay. s.c. injections of 10(6) LNCaP/bcl-2 cells into male nude mice resulted in earlier and larger tumor formation compared to an equivalent injection of parental or control-transfected LNCaP cells. When these variant cell lines were injected into castrated male nude mice, only the LNCaP/bcl-2-transformed cells gave rise to tumors. Moreover, LNCaP/bcl-2 tumors grown in intact male nude mice were refractory to the growth-inhibiting effects of castration demonstrated by parental LNCaP cells. Data obtained in this study demonstrate that the bcl-2 oncoprotein can protect prostate cancer cells from apoptotic stimuli in vitro and suggest that such protection correlates with the ability to form hormone-refractory prostate tumors in vivo.

Genetic Changes in Primary and Recurrent Prostate Cancer by Comparative Genomic Hybridization

Abstract: Genetic changes leading to the development of prostate cancer and factors that underlie the clinical progression of the disease are poorly characterized. Here, we used comparative genomic hybridization (CGH) to screen for DNA sequence copy number changes along all chromosomes in 31 primary and 9 recurrent uncultured prostate carcinomas. The aim of the study was to identify those chromosome regions that contain genes important for the development of prostate cancer and to identify genetic markers of tumor progression. CGH analysis indicated that 74% of primary prostate carcinoma showed DNA sequence copy number changes. Losses were 5 times more common than gains and most often involved 8p (32%), 13q (32%), 6q (22%), 16q (19%), 18q (19%), and 9p (16%). Allelic loss studies with 5 polymorphic microsatellite markers for 4 different chromosomes were done from 13 samples and showed a 76% concordance with CGH results. In local recurrences that developed during endocrine therapy, there were significantly more gains (P < 0.001) and losses (P < 0.05) of DNA sequences than in primary tumors, with gains of 8q (found in 89% of recurrences versus 6% of primary tumors), X (56% versus 0%), and 7 (56% versus 10%), as well as loss of 8p (78% versus 32%), being particularly often involved. In conclusion, our CGH results indicate that losses of several chromosomal regions are common genetic changes in primary tumors, suggesting that deletional inactivation of putative tumor suppressor genes in these chromosomal sites is likely to underlie development of prostate cancer. Furthermore, the pattern of genetic changes seen in recurrent tumors with the frequent gains of 7, 8q, and X suggests that the progression of prostate cancer and development of hormone-independent growth may have a distinct genetic basis. These chromosome aberrations may have diagnostic utility as markers of prostate cancer progression.

Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues

Abstract: Prostate-specific membrane antigen (PSMA) is a trans-membrane glycoprotein recognized by the murine monoclonal antibody (MAb) 7EII-C5.3 both in its native (CYT-351) and immunoconjugate form (CYT-356). Previous studies have shown that tissue expression of PSMA is highly restricted to prostate tissues. In this study, a definitive immunohistochemistry evaluation was performed to assess PSMA expression in prostate tissues. A stain index was established by multiplying the percentage of stained cells by the intensity of the stained cells to provide a quantitative measurement of PSMA expression in the various tissue types. The cellular location of PSMA, its correlation with clinical status, and its comparison with the expression of prostate-specific antigen (PSA) were evaluated. Prostate-specific membrane antigen was found to be highly expressed in most of the normal intraepithelial neoplasia, and the primary and metastatic prostate tumor specimens evaluated. In contrast to PSA, PSMA expression was often heterogeneous with variable staining patterns, ranging from a low-level diffuse cytoplasmic staining in normal prostate epithelium to very intense cytoplasmic and focal membrane staining in high-grade primary carcinomas and metastatic tissues. The predominant cytoplasmic staining was expected because the antigenic epitope of the PSMA transmembrane glycoprotein recognized by MAb 7EII-C5.3 is located in the cytoplasmic domain. Benign prostate tumors, ie, hypertrophy, showed the lowest expression of PSMA with a stain index of 52, compared with stain indexes of 146 and 258 for normal prostate and bone metastatic tissues, respectively. The reason for the apparent down-regulation of PSMA in benign prostate tissue is unknown but may be related to a splicing variant or post-translational modification of PSMA. Expression of PSMA was observed to increase with increasing pathologic grade, but not with clinical stage. Although PSMA was overexpressed in poorly differentiated and metastatic prostate tumors, expression in the primary tumor did not correlate with nodal status, extracapsular penetration, or seminal vesicle invasion. These results suggest that PSMA is not a useful biomarker of disease progression; however, high expression does appear to be associated with the more aggressive prostate carcinoma phenotype. The restricted specificity, differential prostate tissue expression, and overexpression of PSMA in metastatic tissues support the continued study of this unique prostate tumor-associated biomarker for developing new strategies for diagnostic and therapy of prostate cancer.

Evaluation of changes in the size and location of the prostate, seminal vesicles, bladder, and rectum during a course of external beam radiation therapy

Abstract: Purpose : To document the size and location of the prostate, seminal vesicles, bladder, and rectum throughout the course of external beam radiotherapy. The frequency and range of motion of these organs are quantified. Methods and Materials : Ten patients with localized carcinoma of the prostate had conventional simulation followed immediately by a treatment planning computed tomography scan (TPCT 0 ). Once treatment was initiated, each patient had a weekly CT (TPCT 1-N ) before or after his daily treatment. Anatomical structures from CT were delineated on a computer workstation for analysis. The serial CT sets were spatially registered to the initial scan using image correlation software that brings into congruence the bony pelvis of the different scans. The location of the prostate, seminal vesicles, bladder, and rectum on subsequent scans were compared to TPCT 0 , as well as to each other. Results : Prostate volumes were observed to vary by an average of ±10% during the course of radiation therapy, while the seminal vesicle volumes varied by as much as 100%. Bladder and rectal volumes varied by ±30%. Compared to TPCT 0 , movement of the prostate was demonstrated in all patients. Quantitation of the center-of-mass (CM) showed motion of less than 1 mm in the left-right direction, while motion ranging from 0 to ± 1 cm was observed in the anterior-posterior and superior-inferior directions. The individual standard deviations of these motions varied from approximately 1-5 mm. These variations were correlated to changes in the dimensions of the bladder and rectum. Conclusions : Changes in the location of the prostate, seminal vesicles, and normal tissue volumes during the course of radiation therapy occur and have dosimetric consequences that may impact tumor control and normal tissue complication probabilities. Conformal therapy for prostate cancer will require the incorporation of knowledge of the anatomic relationships of these structures as a function of time. Therefore, these uncertainties must be taken into account when designing treatment plans and in considering dose escalation trials.

Implication of cell kinetic changes during the progression of human prostatic cancer

Abstract: The daily percentage of cells proliferating and dying were determined for normal, premalignant, and cancerous prostatic cells within the prostate as well as for prostatic cancer cells in lymph node, soft tissue, and bone metastases from untreated and hormonally failing patients. These data demonstrate that normal prostatic glandular cells have an extremely low but balanced rate of cell proliferation and death (i.e., both /=475 days. As compared to localized prostatic cancer cells, metastatic prostatic cancer cells within lymph nodes or bones of untreated patients have an increase in daily rate of proliferation coupled with a reduction in their daily percentage of cell death, producing net growth rates with a mean doubling time of 33 +/- 4 days and 54 +/- 5 days, respectively. Remarkably, there is no further increase in proliferation in hormonally failing patients, but instead an increase in the daily percentage of androgen-independent prostatic cancer cells dying within soft tissue or bone metastases. These changes result in doubling times which are two to three times longer (i.e., 126 +/- 21 and 94 +/- 15 days) in these lymph node and bone metastatic sites, respectively, compared to similar sites in hormonally untreated patients. These data demonstrate that the daily percentage of proliferation for either androgen-dependent or -independent metastatic prostatic cancer cells is remarkably low (i.e., <3. 0%/day), consistent with why antiproliferative chemotherapy has been of such limited value against such metastatic cells. These results also suggest that prostatic carcinogenesis starts in the second to third decade of life and may require over 50 years for progression to pathologically detectable metastatic disease.

The response of the urinary bladder, urethra, and ureter to radiation and chemotherapy

Abstract: A comprehensive review of the physiological and clinical response of the urinary bladder, ureter, and urethra to radiation and chemotherapy is presented. The clinical syndromes that follow therapy for cancer of the bladder, prostate, and cervix are reviewed in detail. Methods of assessing, scoring, and managing toxicity are discussed.

Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma.

Abstract: Hepatocyte growth factor (scatter factor) and its receptor, the c-met proto-oncogene product (c-MET), have been implicated in embryogenesis, tissue reorganization, and tumor progression Little is known, however, of the expression and functional significance of these molecules in prostatic cells and tissue In this investigation, we assessed the expression of hepatocyte growth factor (HGF) and c-MET in prostatic tissues and cell lines and also determined the effect of purified recombinant HGF on cell proliferation and scattering of prostatic carcinoma cell lines HGF was expressed by human prostatic stromal myofibroblasts in primary culture but not by three human prostatic carcinoma cell lines (LNCaP, DU 145, and PC-3) as assessed by Northern blot analysis HGF was also detected by reverse transcriptase-polymerase chain reaction in both benign and malignant tissues from radical prostatectomy specimens c-MET transcripts were identified by Northern blot in two androgen-insensitive human prostatic carcinoma cell lines (DU 145 and PC-3) but not the androgen-sensitive LNCaP cell line Additional evidence of linkage of androgen responsiveness and c-MET was provided by experiments in which androgen deprivation of normal rat prostates via castration produced a marked up-regulation of c-MET expression as determined by Northern blot and immunohistochemistry c-MET protein was detected by immunohistochemical analysis in a substantial percentage (58 of 128 or 45%) of prostatic carcinomas and was found more often in metastatic growths of human prostatic carcinoma (15 of 20 patients) compared with primary tumors (43 of 108 patients; P < 0005) Moreover, in Dunning R-3327 rat prostatic carcinoma cell lines, c-MET expression was highest in the androgen-insensitive subline with the highest metastatic capacity Purified recombinant human HGF induced dose-dependent cellular proliferation and scattering in the DU 145 carcinoma cell line These data indicate that HGF may function in the prostate gland as a paracrine growth factor, with synthesis by stromal cells and with biological target cells being the epithelial cells Expression of the HGF receptor, c-MET, is up-regulated by androgen deprivation and c-MET appears to be preferentially expressed on androgen-insensitive, metastatic cells, suggesting a possible linkage of c-MET expression with prostatic carcinoma progression

Allelic Loss on Chromosome 8p12–21 in Microdissected Prostatic Intraepithelial Neoplasia

Abstract: The development and progression of human prostate cancer is associated with genetic abnormalities in tumor cells. Inactivation of tumor suppressor genes due to allelic loss is thought to be an important mechanism of gene alteration in prostatic neoplasms. In this study we examined allelic loss on chromosome 8p12-21 in microdissected samples of normal prostatic epithelium, high grade prostatic intraepithelial neoplasia (PIN), and invasive prostate carcinoma from the same patients. Tissue microdissection under direct microscopic visualization procures pure populations of cells of interest, including small lesions such as PIN. Among 30 patients with concomitant cancer and PIN, we found loss of heterozygosity on chromosome 8p12-21 in 63% (34 of 54) of foci of PIN examined and 90.6% (29 of 32) of tumors, suggesting that abnormalities on chromosome 8p12-21 may be important in the early stages of prostatic carcinoma development. Several cases in which multiple foci of PIN from the same patient were sampled showed different patterns of allelic loss. Fifty-five % (16 of 29) of the prostate carcinomas contained a potential precursor PIN focus based on allelic loss pattern. Our results are consistent with the hypothesis that PIN arises multifocally within the prostate gland, and that a subset of these lesions progress to become carcinoma.

Distant Metastases from Prostatic Carcinoma Express Androgen Receptor Protein

Abstract: Nearly all primary prostatic carcinomas have been found to express the androgen receptor (AR) protein, which is the intracellular mediator of androgen action. To gain a better insight into the mechanisms of androgen independence of advanced prostatic carcinoma, it is important to know whether the AR is also present in metastases of androgen-independent tumors. We have assessed the status of the AR and the prostate-specific antigen in 22 metastases of 18 patients with progressive prostate cancer. In 18 cases, the metastases were localized in bone, in 3 cases in the epidural space, and in 1 case in the periosteum. All but one patient had received some kind of endocrine treatment for prostatic carcinoma. Paraffin-embedded tissue sections were stained for the AR following a streptavidinbiotin-peroxidase protocol with the polyclonal antibody PG-21, which is directed against amino acids 1 through 21 of the rat and the human AR. The percentage of AR-positive cells was evaluated on the basis of an arbitrary 4-point scale. All 22 tumor metastases displayed AR positivity. One AR-positive metastatic lesion did not stain for prostate-specific antigen, but in all other metastases, this protein was detected by means of immunohistochemistry. The present study provides evidence that, unlike androgen-independent prostatic carcinoma cell lines, distant prostatic carcinoma metastases do express the AR. These findings indicate that the AR may be involved in the progression of prostate cancer.

In Vivo Gene Therapy with p53 or p21 Adenovirus for Prostate Cancer

Abstract: We introduced the gene for wild-type human p53 or p21, a critical downstream mediator of p53-induced growth suppression, into a p53-deficient mouse prostate cancer cell line using a recombinant adenoviral vector (Ad5CMV-p53 or Ad5CMV-p21). Elevated levels of endogenous mouse p21 mRNA provided evidence for the functional activity of virally transduced p53. Functional activity of viral-transduced p21 was demonstrated through immunoprecipitation of cellular protein extracts, which showed that the viral-transduced p21 associates with cyclin-dependent kinase 2 and was sufficient to down-regulate the activity of the cyclin-dependent kinase by approximately 65%. In vitro growth assays revealed significantly higher growth suppression after Ad5CMV-p21 infection compared to Ad5CMV-p53. In vivo studies in syngeneic male mice with established s.c. prostate tumors demonstrated that the rate of growth and final tumor volume were reduced to a much greater extent in mice that received intratumor injection of Ad5CMV-p21 compared to Ad5CMV-p53. In addition, the survival of host animals bearing tumors that were infected with Ad5CMV-p21, but not Ad5CMV-p53, was significantly extended. These data suggest that Ad5CMV-p21 may be effective as a therapeutic agent for prostate cancer.

A modified technique allowing interactive ultrasound-guided three-dimensional transperineal prostate implantation

Abstract: Purpose : Ultrsound-guided transperineal prostate implantation is a new technique for performing permanent isotope implants of the prostate. The details of the technique are presented to demonstrate its ability to place radioactive seeds three-dimensionally within the prostate gland to achieve uniform dose distribution without the need for complicated preplanning. Methods and Materials : An accurate measurement of the prostate volume is made using biplanar transrectal ultrasound. The total activity to be implanted is derived from a look-up table based on prostate volume. The basic plan is to implant 60–70% of the total activity in the peripheray of the gland and the remaining activity in the interior of the gland. The ultrasound transducer provides visualization of the prostate through transverse, longitudinal and oblique cuts and allows for accurate placement of implant needles, approximately 1 cm apart. In addition, these needles can be moved through teh prostate under constant visualization, thus allowing for precise seed placement. Results : The setup of the transrectal ultrasound device as well as prostate volume measurements are performed in 10 to 15 min. The actual placement of the needles and seed implantation takes 1 to 1.5 h to perform. Postimplantation dosimetric evaluation is performed using orthogonal x-ray films and 3 mm thick CT slices taken at 3 mm intervals. This evaluation has confirmed accurate seed placement within the prostate gland. Conclusion : Interactive ultrasound guided transperineal prostate implantation is a fast and accurate method of performing permanent radioactive isotope prostate implants.

Detection of circulating tumor cells in patients with localized and metastatic prostatic carcinoma: clinical implications.

Abstract: PURPOSETo determine the frequency with which prostate-specific antigen (PSA)-positive cells can be detected in the peripheral blood of patients with prostatic cancer in different stages and with different sensitivities to hormonal therapy.PATIENTS AND METHODSPeripheral blood from 107 men with prostatic cancer and 27 non-prostate cancer controls was analyzed for PSA mRNA using reverse-transcriptase polymerase chain reaction (RT-PCR) and Southern blotting.RESULTSThe lower limit of detection was one PSA-producing cell diluted into 1 x 10(6) blood mononuclear cells. The test detected PSA mRNA in four of 25 patients (16%) with clinically organ-confined (T1-2) disease, three of 10 (30%) with T3-4 or N+ tumors, and 25 of 72 (35%) with distant metastases. None of the control samples were positive. An increase in positivity was observed with increasing PSA levels. Within the subgroup of patients with distant metastases, positivity was observed in six of 16 patients (38%) with normal or undetectable PSA levels afte...