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Prostate adenocarcinoma using Gleason scores correlates with prostate-specific antigen and prostate acid phosphatase measurements.

To evaluate a relationship between Gleason scores of histopathology of prostate carcinoma and concurrent serum prostate-specific antigen (PSA) and prostate acid phosphatase (PAP) values, 65 men with prostate carcinoma were studied. These patients' cumulative Gleason scores were obtained by totaling the primary and secondary patterns, resulting in two groups: 42 patients received high (6-10) and 23 received low (2-5) Gleason scores. Serum PSA and PAP values were measured by radioimmunometric assay 1 to 7 days before surgical procedures or biopsy for prostate carcinoma. Mean serum PSA for patients in the high Gleason score group was 134.39 ng/mL (normal range: 0 to 4), and the mean serum PSA for patients in the low Gleason score group was 23.62 ng/mL. Mean serum PAP for patients with high scores was 28.08 ng/mL (normal range: 0 to 5), and the mean serum PAP for patients with low scores was 18.19 ng/mL. Patients with high Gleason scores showed significantly greater elevation of serum PSA than those with low Gleason scores (P = .047), using two samples to test for groups having unequal variants. Prostate acid phosphatase levels of patients with high scores were not significantly higher than the levels in patients with low scores (P = .60). These results indicate that PSA levels but not PAP levels correlate with Gleason scores.

Acid Phosphatase↗

Prostate-specific antigen and prostate-specific acid phosphatase in neuroendocrine cells of prostate cancer.

Prostate-specific antigen is a specific immunohistochemical marker of benign prostatic epithelium and prostate cancer. A subpopulation of neuroendocrine cells seen in 50% of cancers do not produce this protein marker. These cells appear to secrete prostate-specific acid phosphatase. This finding may explain the marked variation in serum prostate-specific antigen levels in all stages of prostate cancer.

Acid Phosphatase↗

A complex between prostate-specific antigen and alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer.

We have studied the forms of prostate-specific antigen (PSA) in serum of patients with prostatic cancer and benign prostatic hyperplasia. Fractionation of serum by gel filtration and assay of the fractions for PSA showed that a considerable part of the PSA immunoreactivity in serum consisted of complexes that were larger than PSA. The complexes were assayed by time-resolved immunofluorometric assays based on an antibody against PSA on the solid phase and europium-labeled antibodies against various protease inhibitors as indicator antibodies. In addition to its monomeric form, PSA was found to occur in complex with alpha 1-antichymotrypsin. The proportion of the alpha 1-antichymotrypsin complex was a major form of PSA and it increased with increasing PSA concentrations, being over 85% at PSA levels exceeding 1000 micrograms/liter. A complex with alpha 1-protease inhibitor was also observed in serum of patients with prostatic cancer and very high levels of PSA. Complexes with alpha 2-macroglobulin and inter-alpha-trypsin inhibitor were detected, but their concentrations were low and similar in sera of cancer patients, normal men, and normal women, suggesting that they were not prostate derived. Commercial immunoradiometric assays for PSA were found to measure free PSA and its complexes with alpha 1-antichymotrypsin but not the complexes with alpha 2-macroglobulin and inter-alpha-trypsin inhibitor. The proportion of the PSA-alpha 1-antichymotrypsin complex was higher in patients with prostatic cancer than in those with benign hyperplasia. Therefore, assay of the complex had a higher sensitivity for cancer than assay of total PSA immunoreactivity.

Antigens, Neoplasm↗

Diagnostic value of prostatic acid phosphatase and prostate-specific antigen in patients with prostatic cancer.

To compare the clinical usefulness of the measurement of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) in serum of patients with prostatic carcinoma, we studied 128 patients with prostatic pathology, sixty (46.9%) of whom had prostatic cancer. Receiver-operating characteristics (ROC) curves were constructed and the underlying areas were calculated and compared to study clinical efficiency of the two markers regardless of the cutoff level selected. The area for PSA (0.90 +/- 0.30) was significantly higher (p less than 0.001) than that of PAP (0.71 +/- 0.05) showing that PSA was a better discriminator of the patients with or without prostatic cancer. The maximal clinical efficiency of the two tests at selected cutoff levels (0.8 U/L for PAP and 10 micrograms/L for PSA) was 0.787 and 0.883, respectively, confirming the superiority of PSA. However, the associated determination of the two markers improved the clinical specificity with no false-positive cases.

Acid Phosphatase↗

Studies on carcinogenesis of human prostate. II. Long-term explant culture of normal prostate and benign prostatic hyperplasia: light microscopy.

Light microscopic and histochemical changes in normal human prostate and benign prostatic hyperplasia (BPH) during long-term explant culture were characterized. Normal human prostate obtained at immediate autopsy of young adults or BPH obtained at the time of surgery were maintained in explant culture as long as 24 weeks. Morphologic alterations in glandular epithelium and stroma in response to culture conditions were assessed by light microscopy and histochemistry of mucosubstances. The histologic and histochemical responses of normal prostate and BPH to in vitro conditions were essentially identical. Within 1 week, secretory epithelial cells became necrotic and sloughed into acinar lumina. Remaining epithelial cells proliferated, repopulated acinar structures, and migrated onto explant surfaces forming a new well-differentiated epithelium characterized by synthesis and secretion of neutral and acidic mucosubstances. During subsequent periods in vitro, synthesis and secretion of mucosubstances gradually diminished whereas the stroma and deep glandular structures became necrotic. Our observations suggest that cells comprising the new epithelium in cultured explants of normal human prostate and BPH are derived from prostatic basal cells.

Adolescent↗

Prospective evaluation of prostate specific antigen and prostate specific antigen density in the detection of carcinoma of the prostate: ethnic variations.

PURPOSE: We evaluated prospectively the ethnic variations in prostate specific antigen (PSA) and prostate specific antigen density in the detection of carcinoma of the prostate. MATERIALS AND METHODS: A total of 297 consecutive patients with an elevated serum PSA and/or abnormal digital rectal examination underwent transrectal ultrasound with lesion directed and systematic biopsy (6 if the prostatic volume was 50 cc or less and 12 if it was greater than 50 cc). Receiver operating characteristic curves, predictive values and likelihood ratios were calculated for PSA and PSA density for white and black patients. Ethnic analysis was performed for the entire group, patients with a normal digital rectal examination, and those with a normal digital rectal examination and PSA of 4 to 10 ng./ml. RESULTS: Of the 297 patients 131 (44%) had cancer, including 48 of 97 black (50%) and 83 of 200 white (42%) patients. Median PSA, PSA density and prostate size did not differ between the positive or negative biopsy groups, or between the ethnic groups in any of the analyses. If all digital rectal examinations were considered PSA density was superior to PSA by receiver operating characteristic analysis for cancer detection in both ethnic groups when all values or PSA of 4 to 10 ng./ml. were considered. However, the significance was lost if only patients with a normal digital rectal examination were considered. In general, predictive values were greater in black patients. Likelihood ratios for a negative test result in black patients demonstrated significant changes in the post-test probability if a PSA density cutoff of 0.1 was used to determine the need for biopsy. Many unnecessary biopsies could be avoided and few cancers would be missed. CONCLUSIONS: A PSA density cutoff of 0.1 may be warranted in determining the need for prostate biopsy in black men with a normal digital rectal examination.

Aged↗

The effect of digital rectal examination, flexible cystoscopy and prostatic biopsy on free and total prostate specific antigen, and the free-to-total prostate specific antigen ratio in clinical practice.

PURPOSE: We evaluated the effects of common urological maneuvers on serum free prostate specific antigen (PSA) and established guidelines for clinical practice. MATERIALS AND METHODS: Total and free PSA, and free-to-total PSA ratio were determined in 82 men with lower urinary tract symptoms before and 30 minutes after 3 different prostatic manipulations: 1) digital rectal examination (36 cases), 2) flexible cystoscopy (26) and 3) transrectal ultrasound guided prostatic biopsy (20). PSA forms were measured with Hybritech Tandem-R assays. RESULTS: Cystoscopy had no effect on total PSA, while digital rectal examination had a slight, statistically significantly positive effect and biopsy uniformly increased total PSA (geometric mean ratio 2.43, t = 5.08, p <0.001). Free PSA was increased by digital rectal examination (geometric mean ratio 1.67, t = 4.25, p <0.001), prostatic biopsy (geometric mean ratio 4.80, t = 7.48, p <0.001) and cystoscopy (geometric mean ratio 1.21, t = 2.51, p = 0.019). There was a significant increase in free-to-total PSA ratio after each maneuver. The rate of change in free PSA and free-to-total PSA ratio after biopsy differed between patients with benign and malignant histological findings. CONCLUSIONS: Free PSA and free-to-total PSA ratios are altered by all forms of prostatic manipulation. The PSA response to manipulation may be different in patients with prostatic malignancy. Phlebotomy must precede digital rectal examination in the clinical and research setting to avoid misleading results.

Adult↗

Expression-patterns of the RNA component (hTR)and the catalytic subunit (hTERT) of human telomerase in nonneoplastic prostate tissue, prostatic intraepithelial neoplasia, and prostate cancer.

BACKGROUND: Telomerase, a ribonucleoprotein, is composed of a RNA component (hTR) and two protein subunits. One of these subunits, the catalytic subunit (human telomerase reverse transcriptase, hTERT), represents a reverse transcriptase. hTERT-expression is closely correlated with telomerase activity. The telomerase is thought to be involved in immortalization process. By adding hexamic repeats to the end of chromosomal DNA, the telomeres, the enzyme is able to stop progresssive telomeric DNA loss that occurs during cell division due to the end replication problem that stops the mitotic clock. METHODS: Expression-patterns of hTR using radioactive in situ hybridization with (35)S-labelled RNA probes were compared with immunhistochemical staining for hTERT in 14 cases of archival paraffin-embedded samples of normal prostatic tissue, high-grade prostatic intraepithelial neoplasia (PIN), prostatic cancer, and one atypical adenomatous hyperplasia (AAH). Beside the expression-patterns each telomerase component was evaluated semiquantitatively. RESULTS: hTERT and hTR can be found in nonneoplstic tissue and are upregulated in premalignant transformated lesions. AAH showed no hTERT-expression and low hTR-expression. There is a heterogenous expression within prostatic carcinomas. CONCLUSIONS: No association was observed between the grade of the tumour differentiation and semiquantitative levels of hTR- or hTERT-expression. Telomerase is of limited value for the diagnostic of malignant or benign lesions in prostate.

Carcinoma↗

PSP94 expression after androgen deprivation therapy: a comparative study with prostate specific antigen in benign prostate and prostate cancer.

PURPOSE: To examine the clinical use of PSP94 (prostate secretory protein of 94 amino acids) as an androgen independent marker, we conducted a comparative study of prostate samples including benign tissue and cancers which did and did not have androgen deprivation. MATERIALS AND METHODS: Among 163 radical prostatectomy cases 75 had androgen deprivation before operation, while surgery was performed in the remainder without prior hormone treatment. Considering the pathological up grading following hormone therapy, contiguous sections from radical prostatectomy samples were stained for PSP94 and prostate specific antigen (PSA) by immunohistochemistry, and equivalent tumor foci were evaluated by assessing the intensity and extent of the staining. RESULTS: In untreated benign prostate tissue PSP94 and PSA staining was positive and identical in all sections in the no pretreatment group. However, PSP94 expression in the androgen deprivation group was significantly higher than PSA in intensity (p = 0.0005) and extent (p = 0.034). In untreated cancer cases PSP94 intensity and extent demonstrated strong inverse association with Gleason grade (p <0.0001). In contrast, PSA expression was high in every grade, resulting in no statistical association with tumor grade. In the androgen deprivation group PSA staining was decreased in every grade compared to the no pretreatment group. On the other hand, PSP94 expression was decreased in grade 3 tumor foci but increased in grades 4 and 5 tumor foci compared with samples of the corresponding grade in the no pretreatment group (p = 0.0034). CONCLUSIONS: PSP94 expression in benign prostate persists under androgen deprivation compared to PSA. PSP94 synthesis in high grade tumor appears to be activated in the absence of androgen stimulation, indicating the possible alternative pathways in the regulation of PSP94.

Adenocarcinoma↗

[Importance of specific prostatic antigen to prostatic volume ratio in the selection of patients for ultrasonography-guided biopsy of the prostate].

US-guided biopsy was performed in 94 patients with suspected lesions at transrectal US. Histology demonstrated carcinoma in 43 cases, benign hyperplasia in 44, and prostatitis in 7. In all cases the prostate specific antigen (PSA) was calculated, by means of US, together with prostatic volume (V). PSA was related to the corresponding gland volume, which resulted in PSA/V index. Subsequently, histology was correlated with both PSA value and PSA/V ratio. Our study showed PSA/V ratio to have higher sensitivity and specificity than absolute PSA value in the diagnosis of prostatic carcinoma. The authors believe prostate US-guided biopsy to be: a) necessary when the suspected area has PSA/V ratio greater than 0.15, and especially when PSA/V greater than 0.30; b) not indicated when echostructural alterations are associated with PSA/V less than 0.15, because they are most frequently due to benign lesions. The combined use of PSA/V ratio and US is therefore suggested to select the patients in whom biopsy is to be performed.

Aged↗

[The role of the absolute value and "density" of the prostate-specific antigen estimated echographically in the selection of patients to undergo a biopsy in suspected prostatic carcinoma. A comparison between PSA, palpation and echography in 95 patients undergoing echo-guided endorectal prostatic biopsy].

We retrospectively reviewed the findings relative to 95 patients with known prostate specific antigen (PSA) values who had undergone digital rectal examination, transrectal US and US-guided biopsy for suspected prostate carcinoma. Histology (48 adenocarcinomas, 26 BPHs, 12 inflammations and 9 negatives) was compared with results from rectal examination, prostate US, PSA values and "density" (PSA/prostatic volume, as measured with US). PSA values < 4 ng/ml exhibited 90% negative predictive value and PSA > 10 ng/ml 70.8% positive predictive value. In the intermediate range (4-9.9 ng/ml) the positive predictive value of PSA was 44.4% and its negative predictive value was 55.5%. PSA density did not affect predictive values in the two groups with PSA < 4 and > 10 ng/ml, while in the intermediate 4-9.9 ng/ml group, positive predictive value raised to 62.5% and negative predictive value to 81.8%, thus increasing the specificity of PSA values and US findings. Our results suggest that PSA should be the examination of choice in the patients with prostatic disease. Follow-up with PSA dosage after one year may be suggested when PSA < 4 ng/ml. PSA density can be helpful in patients with PSA values ranging 4-9.9 ng/ml; biopsy should be performed when the index > 0.15, while follow-up at 6 months should be performed when the index < 0.15. PSA values > 10 ng/ml require further evaluation with rectal examinations, prostate US and US-guided biopsy. Random biopsies are suggested when PSA values are > 20 ng/ml.

Adenocarcinoma↗

The value of prostatic acid phosphatase and prostate specific antigen as serum markers in carcinoma of the prostate.

The value of prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) as serum markers in carcinoma of the prostate (CaP) was investigated in this study. A group of 75 patients entered this trial, 25 with CaP, 25 with benign prostatic hyperplasia (BPH) and 25 with urologic disorders other than prostatic diseases. In the CaP group, PAP was above normal levels in 48% of the patients and PSA in 92%. In the BPH group these rates were 20% and 72%, respectively. No elevation was detected in the third group. In CaP patients with capsular invasion, PAP and PSA levels were above normal in 25 and 87.5%. In metastatic carcinoma, PAP was high in 75% and PSA in 100%. Our study reveals that neither of these markers is useful in the initial diagnosis of CaP. Though PSA seems to be more sensitive, it is not more specific than PAP.

Acid Phosphatase↗

Prostate volume and prostate-specific antigen in the absence of prostate cancer: a review of the relationship and prediction of long-term outcomes.

BACKGROUND: The risk for long-term outcomes associated with benign prostatic hyperplasia (BPH) has not been well characterized. Untreated, BPH can lead to complications and negative outcomes, such as deterioration of bladder function, urinary tract infection, acute urinary retention (AUR), and surgery. METHODS: A literature review was conducted to summarize the results of studies investigating the relationship of prostate volume and PSA with prediction of long-term outcomes in the absence of prostate cancer. RESULTS: In the studies reviewed, men with moderate to severe symptoms, depressed uroflow, prostatic enlargement and elevated PSA were at greater risk for developing subsequent AUR or surgery. Men with prostatic enlargement had a 3-fold higher risk for acute urinary retention and were 4 times more likely to have had any treatment for BPH. CONCLUSIONS: The results of these studies may assist physicians in discussing treatment options as well as long-term complications with patients.

Clinical Trials as Topic↗

Differential responsiveness of prostatic acid phosphatase and prostate-specific antigen mRNA to androgen in prostate cancer cells.

Androgens regulate the expression of both human prostatic acid phosphatase (PAcP) and prostate-specific antigen (PSA), two major prostate epithelium-specific differentiation antigens. Due to the important role of these two enzymes as prostate epithelium differentiation markers, we investigated their regulation of expression at the mRNA level in LNCaP human prostate carcinoma cells. Interestingly, phenol red, a pH indicator in the culture medium, promoted cell growth. To eliminate this non-specific effect, a phenol red-free, steroid-reduced medium was utilized. When high-density cells were grown in that medium, 5alpha-dihydrotestosterone (DHT) suppressed PAcP but stimulated PSA. However, tumor promoter phorbol ester 12-o-tetradecanoyl phorbol-13-acetate (TPA) functioned as a potent inhibitor of both PAcP and PSA expression. Prolonged treatment with DHT as well as TPA resulted in a similar down-regulation of protein kinase C and cellular PAcP activities. Thus, the levels of PAcP and PSA mRNA are differentially regulated by androgens in LNCaP cells.

Acid Phosphatase↗

Increased discrimination between benign prostatic hyperplasia and prostate cancer with equimolar total prostate specific antigen measurement.

Although prostate specific antigen (PSA) is widely used in the discrimination of benign prostatic hyperplasia (BPH) and prostate cancer, its diagnostic value is controversial due to an appreciable false positive rate. In the present study, we compared a recently introduced assay method, equimolar PSA measurement, to non-equimolar PSA measurement and also determined the diagnostic value of percent free PSA with changing total PSA (tPSA) measurements. Between April 1999 and December 2001, the sera of 61 patients with BPH and 41 with prostate cancer were examined. Total PSA and free PSA was determined using the Immulite 2000 assay system, whereas equimolar tPSA measurement was performed using Bayer PSA Q for the Chiron ACS 180 system. Comparative analysis of the two different assays revealed better diagnostic sensitivity and specificity values for equimolar tPSA measurement, which in turn would have led to 10% of the patients avoiding an unnecessary biopsy. Additionally, percent free PSA with the changing denominator of tPSA assays showed that the free PSA/equimolar tPSA ratio was the best tumor marker among the studied forms of PSA. It was concluded that equimolar tPSA measurement using recombinant Fab fragments is superior to the classical measurements with monoclonal antibodies, and that the use of percent free PSA with the equimolarly measured tPSA has better sensitivity and specificity in the discrimination of benign and malignant diseases of the prostate.

Aged↗

Tissue-specificity of prostate specific antigens: comparative analysis of transcript levels in prostate and non-prostatic tissues.

Activation of immune defense mechanisms against tumor antigens appears to be a promising therapeutic option for advanced prostate cancer (PCa). Specific immunotherapy critically depends on target antigens that are selectively expressed in the tumorous and optional in the normal prostate tissue in sufficient amounts. Although several prostate antigens have been described and some have already been used in clinical trials, a detailed comparative evaluation of their tissue-specificity and expression levels is still lacking. We determined the transcript levels of eight prostate targets (PSA, PAP, PSCA, PSGR, Prostein, PSMA, AIbZIP, trp-p8) in 16 different tissues by quantitative PCR and calculated a tissue-specificity index (TSI) for each molecule. Besides a preferential expression in prostate for all targets, striking differences in the expression levels and TSI were revealed which may be important for the selection of appropriate antigens for immunotherapy of PCa.

Acid Phosphatase↗

Phytoestrogen tissue levels in benign prostatic hyperplasia and prostate cancer and their association with prostatic diseases.

OBJECTIVES: To compare phytoestrogen tissue levels in men with small-volume benign prostatic hyperplasia (BPH), large-volume BPH, and prostate cancer (PCa). METHODS: Prostatic tissue samples of men consuming a Western diet who underwent surgery for BPH (n = 63) or PCa (n = 31) were collected and frozen at -40 degrees C. In the tissue samples, the enterolactone and genistein levels were determined in duplicate by monoclonal antibody-based immunoassays. We subsequently compared the tissue levels in patients with BPH and PCa and studied the impact of enterolactone and genistein on prostate volume. RESULTS: The enterolactone tissue levels were comparable in patients with BPH and PCa and revealed no correlation to prostate volume. The genistein tissue levels tended to be lower in patients with PCa (median 8.4 ng/g dry weight) compared with the entire BPH group (11.0 ng/g dry weight; P = 0.072). In addition, the genistein tissue levels were significantly greater in men with small-volume BPH (median 20.9 ng/g dry weight) compared with those with large-volume BPH (8.8 ng/g dry weight; P = 0.023). CONCLUSIONS: Our data suggest an involvement of genistein in the pathogenesis of BPH and, possibly, of PCa. The impact of enterolactone is currently unknown.

4-Butyrolactone↗

Prostate specific antigen and prostatic acid phosphatase immunoreactivity as prognostic indicators of advanced prostatic carcinoma.

To determine whether the prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) immunoreactivities in prostatic carcinoma are reliable prognostic factors, the PSA and PAP immunohistochemical distribution was examined in needle biopsy specimens of 80 patients with advanced prostatic carcinoma. Our results indicated a higher cancer-specific survival rate in patients with a greater PSA or PAP immunostaining. Furthermore, a multivariate analysis of possible prognostic factors, that is patient age, clinical stage, Gleason score, serum PAP, PSA and PAP immunostaining scores, and the initial treatment, has confirmed that the difference in PAP immunoreactivity is the most important prognostic factor (p < 0.01) for advanced prostatic carcinoma, with the Gleason score (p = 0.06), clinical stage (p = 0.09) and PSA immunoreactivity (p = 0.48) being the second, third and fifth prognostic factors, respectively.

Acid Phosphatase↗