Evaluation of specific antigen and prostatic acid phosphatase specificity. Study of false values

We assayed prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) serum levels in 1305 subjects without malignant prostatic pathology by double antibody RIA I125 to evaluate their specificity. When we set a second upper normal limit of 10 ng/ml for PSA and 2.5 ng/ml for PAP there was a significant increase of specificity. There were 2 and 3.7% false positive results in non-prostatic benign pathologies, 1.8 and 7.9% in non-prostatic malignant, 3.5 and 4.7% in non-complicated benign prostatic hypertrophy (BPH) and 3.3% for both in chronic prostatitis. In patients with complicated BPH and acute prostatitis the results were 64.8 and 24% for PSA and 20 and 16% for PAP. In conclusion, PSA is more specific than PAP in patients without acute inflammatory pathology of the prostate; the high rate of false positive values in the latter excludes its usefulness in these patients as diagnostic tumoral markers.     

The contribution of prostatic acid phosphatase and prostatic specific antigen in the diagnosis of prostatic cancer

Prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) were measured by immunochemical methods using test preparations from two different companies. In 66 patients with benign hyperplasia of the prostate a good correlation was found only between PSA levels (orthogonal regression analysis: y = 1.77 x -0.68; r = 0.995). Discrimination analysis between benign hyperplasia and new prostatic cancer (28 patients), using ROC curves, revealed a sensitivity for prostatic cancer of about 30 percent using both PAP methods and of about 58 percent using both PSA methods at the 95-percentile of benign hyperplasia. The PSA methods were both more sensitive in detecting prostatic cancer than the PAP methods.     

血清PSA、EGF在不同类型良性前列腺增生患者中表达意义及其与术后疾病转归的相关性分析

摘要 目的：分析血清前列腺特异抗原（PSA)、表皮生长因子（EGF)在不同类型良性前列腺增生患者中低表达意义及其与术后疾病转归的相关性。方法：选择自2020年1月至2022年12月在我院接受手术治疗的128例良性前列腺增生患者作为研究对象,根据术后病理活检结果进行分组,间质结节组（16例）、腺肌性结节组（32例）、纤维腺瘤性结节组（12例）、腺性结节组（30例）和混合结节组（38例）,其中以间质增生为主60例、以腺体增生为主68例。检测所有患者血清PSA、EGF的表达水平,以术后6个月的国际前列腺症状评分（IPSS评分）<8分判定为预后良好,分析血清PSA、EGF在预后良好组与预后不良组之间的差异性及与IPSS评分的关系。结果：血清PSA、EGF表达水平在间质结节组、腺肌性结节组、纤维腺瘤性结节组、腺性结节组和混合结节组间比较有差异（P<0.05）;以腺体增生为主的良性前列腺增生患者血清PSA、EGF表达水平均明显高于以间质增生为主的患者（P<0.05）;经ROC曲线分析,血清PSA联合EGF预测以腺体增生为主的良性前列腺增生的敏感度为86.42%,特异度为65.34%,AUC为0.930;所有患者均获得随访6个月,预后良好98例、预后不良30例;预后不良组血清PSA、EGF表达水平均明显高于预后良好组（P<0.05）;经Pearson相关性分析,良性前列腺增生患者血清PSA、EGF表达水平均与IPSS评分呈负相关（r值分别为-0.348、-0.417,P值均为0.000）。结论：血清PSA、EGF在不同病理类型良性前列腺增生患者中表达差异显著,以间质增生为主的患者,以腺体增生为主的患者血清PSA、EGF表达水平更高,两者均与术后疾病转归密切相关,值得临床予以重视。     

Prostate-specific antigen and 17-hydroxylase polymorphic genotypes in patients with prostate cancer and benign prostatic hyperplasia

We investigated the association of prostate cancer (PCa) and benign prostatic hyperplasia (BPH) with genetic polymorphisms in prostate-specific antigen (PSA) (-158 G/A) and 17-hydroxylase (CYP17) (-34 T/C) genes in a Turkish population. In this study, we investigated the distribution of these polymorphisms in 148 PCa patients, 136 BPH patients, and 102 healthy individuals as controls. The polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism assay. Genotype and allele frequencies were calculated, and their associations with PCa or BPH risk are assayed. The frequency of PSA gene GA and GG genotypes was significantly higher in PCa patients than in controls (p = 0.017 and p = 0.019, respectively). GG genotype was also associated with BPH (p = 0.033). In a case analysis, according to Gleason score, the association of PSA gene GG genotype with Gleason score >7 was near to statistical significance (odds ratio, 2.94; 95% confidence interval, 0.95-9.28). There was also an association between CYP17 polymorphism and BPH (p = 0.004). No association was observed between PCa and CYP17 gene polymorphism. These data demonstrate that PSA gene promoter variation may play a significant role in the development of PCa and BPH, and that CYP17 gene polymorphism may be associated with BPH in the Turkish population studied.     

Clinical utility of prostatic specific antigen and prostatic acid phosphatase serum levels in monitoring prostate cancer

We analysed 696 prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) serum samples by double antibody radioimmunoassay (RIA)I125 in the follow-up of 122 patients with prostate cancer under treatment. PSA levels were significantly correlated to response to treatment, whereas PAP results did not differentiate patients with partial or complete remission. Progression of the disease was detected in 95.2 and 85.4% of PSA and PAP samples, and increased to 99.9% using both simultaneously. On the whole, PSA was better than PAP in monitoring prostate cancer, and the efficacy was greater using both markers together.     

Clinical behaviour of prostatic specific antigen and prostatic acid phosphatase: a comparative study

We assayed prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) serum levels in 1383 patients using a double antibody radioimmunoassay (RIA) I125. Establishing the upper normal limit in 10 ng/ml PSA and 2.5 ng/ml for PAP, the false positive results were only 1.9 and 5.1 percent in men with non-prostatic benign or malignant pathology and respectively 0 and 2.2 percent in women. We detected false positive levels for these two tumoral markers in 3.5 and 4.7 percent of patients with non-complicated benign prostatic hypertrophy, 64.8 and 19.2 percent in complicated benign prostatic hypertrophy, 24 and 16 percent in acute prostatitis and 3.3 percent in chronic prostatitis. The sensitivity in patients with prostate cancer was 87.2 percent for PSA and 64.1 percent for PAP, and there was a better correlation with PSA than PAP for tumoral spread and histological grading. Finally, clinical efficacy was higher with PSA and was no better when both markers were assayed.     

Contribution of Genetic Variation rs266882 to Prostate-Specific Antigen Levels in Healthy Controls with Serum PSA Below 2.0 ng/ml

We evaluated the impact of genetic variation in the prostate-specific antigen (PSA) gene (rs266882) on serum PSA levels in healthy men as well as risk factors for benign prostate hypertrophy (BPH) and prostate cancer. The study population comprised 91 men with PSA levels below 2.0 ng/ml as healthy controls, 78 men with PSA 2–10 ng/ml as a BPH group, and 128 prostate cancer patients, all in Korea. DNA was amplified by polymerase chain reaction and the product was sequenced. We found that PSA levels were associated with a G/A polymorphism only in healthy controls. The transition, however, was not associated with PSA levels of BPH and cancer patients, nor was it a risk factor. In conclusion, this genetic factor is important for determining serum PSA levels in the naive group, whereas the disruption of prostatic architecture in BPH or prostate cancer may be a major determining factor for PSA levels.     

Serial lectin affinity chromatography with concanavalin A and wheat germ agglutinin demonstrates altered asparagine-linked sugar-chain structures of prostatic acid phosphatase in human prostate carcinoma

Differences between human prostate carcinoma (PCA, five cases) and benign prostatic hyperplasia (BPH, five cases) in asparagine-linked (Asn) sugar-chain structure of prostatic acid phosphatase (PAP) were investigated using lectin affinity chromatography with concanavalin A (Con A) and wheat germ agglutinin (WGA). PAP activities were significantly decreased in PCA-derived PAP, while no significant differences between the two PAP preparations were observed in the enzymatic properties (Michaelis–Menten value, optimal pH, thermal stability, and inhibition study). In these PAP preparations, all activities were found only in the fractions which bound strongly to the Con A column and were undetectable in the Con A unbound fractions and in the fractions which bound weakly to the Con A column. The relative amounts of PAP which bound strongly to the Con A column but passed through the WGA column, were significantly greater in BPH-derived PAP than in PCA-derived PAP. In contrast, the relative amounts of PAP which bound strongly to the Con A column and bound to the WGA column, were significantly greater in PCA-derived PAP than in BPH-derived PAP. The findings suggest that Asn-linked sugar-chain structures are altered during oncogenesis in human prostate and also suggest that studies of qualitative differences of sugar-chain structures of PAP might lead to a useful diagnostic tool for PCA.     

Prostate-specific antigen levels among cirrhotic patients

PURPOSE: The aim of this study was to determine serum prostate-specific antigen (PSA) levels in patients with liver cirrhosis. PATIENTS AND METHODS: Between January 1995 and August 2001, 216 men with cirrhosis were evaluated. The extent of their liver disease was classified according to the Child-Pugh classification. Serum PSA levels were measured with the Hybritech Tandem-R RIA method and matched with age-related reference PSA levels. Digital rectal examination (DRE) was performed in all patients. Patients with elevated PSA levels and/or abnormal DRE were recommended to undergo further assessment including transrectal ultrasonography (TRUS) and biopsy performed by an urologist. RESULTS: Two hundred and sixteen men (mean age 54.09 +/- 9.09 years, range 25-76) with cirrhosis were examined. Their mean PSA value was 0.57 +/- 0.84 ng/mL and tended to be lower than in the normal population. The degree of PSA decrease was found to parallel the severity of the liver disease (p=0.002). The mean serum PSA level increased with each age decade in a statistically significant manner (p<0.001). Four patients (three with elevated PSA values) underwent prostate biopsy. Three biopsies were positive for prostate cancer, the other showed evidence of benign prostatic hyperplasia (BPH). CONCLUSION: Serum PSA is influenced by the severity of liver disease and its levels tend to be lower in cirrhotic patients than in the normal population. However, serum PSA can still be considered a reliable marker in the clinical management of prostatic disease in patients with cirrhosis.     

Steroids inversely affect the biosynthesis and secretion of human prostatic acid phosphatase and prostate-specific antigen in the LNCaP cell line

In order to elucidate the mechanism of androgen-regulation of genes expressed only in the prostate gland, the effects of steroid hormones on the biosynthesis and secretion of human prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) were studied in the human prostatic carcinoma cell line, LNCaP. This cell line produces PAP and PSA, both of which were found to be similar to the proteins purified from and located in human prostatic tissue, as shown by Western blot analysis. The synthetic androgen, R1881, regulated the biosynthesis of these two important tumour marker proteins inversely: the amount of PSA released into the medium was increased to 506%±100 of the control levels, while that of PAP was decreased to 26%±3, in 7 days. These effects were dependent on the concentration of the steroid in the growth medium. The androgen-dependent changes observed in the amounts of the secreted proteins were correlated with alterations in their intra-cellular levels. LNCaP cells were found to have very different capacities for secreting PAP and PSA. Whereas the measurable, cellular amounts of PSA and PAP were of similar magnitudes, much larger amounts of PSA than PAP were secreted into the medium. PSA was also found to be more stable than PAP in the culture medium of the LNCaP cells. Other steroids could elicit effects on PAP and PSA biosynthesis similar to those induced by R1881, and the combined effects of effective concentrations of these steroids were undistinguishable from those caused by each one of them separately, suggesting that all these compounds compete for binding to the same modified androgen receptors of the LNCaP cells. Thus, our results confirm the observations of the altered nature of the LNCaP androgen receptors, and demonstrate the ability of these ligands to produce changes in the expression of androgen-dependent prostatic genes. The fact that the changes observed at the protein level were accompanied by increased levels of PSA mRNAs and by decreased levels of PAP mRNA in steroid-treated cells, suggests that one of the targets of androgen and steroid action in the regulation of these genes is at the mRNA level.     

Tumor markers in patients with chronic renal failure.

In order to evaluate the specificity of tumor markers in chronic renal failure, we have determined serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA 19.9), carbohydrate antigen 50 (CA 50), alphafetoprotein (AFP), neuron-specific enolase (NSE), prostatic acid phosphatase (PAP), prostatic specific antigen (PSA), squamous cell carcinoma antigen (SCC), carbohydrate antigen 15.3 (CA 15.3) and carbohydrate antigen 125 (CA 125) in 30 patients with chronic renal failure and in 36 hemodialyzed patients without clinical evidence of neoplasia. CEA, CA 50, NSE and SCC frequently show increased serum levels, suggesting a renal metabolism, while others remain, generally, within the normal levels.     

Gene expression and prostate specificity of human prostatic acid phosphatase (PAP): evaluation by RNA blot analyses.

A fragment of a complementary DNA (cDNA) clone for human prostatic acid phosphatase (PAP) (EC 3.1.3.2.) was used to study the expression of corresponding mRNA in human tissues. The specificity of its expression in benign prostatic hyperplasia (BPH) and prostatic carcinoma tissues were indicated in RNA blot analyses. The PAPcDNA probe did not recognize any specific mRNAs in RNAs extracted from human liver cancer, lung cancer, pancreatic cancer, placenta, breast cancer cells (MCF-7), mononuclear blood cells or acute promyelocytic leukemia cells (HL-60), according to Northern blot analysis. mRNA for PAP was detected in the androgen-dependent human prostatic cancer cell line LNCaP, but not in the androgen-insensitive human prostatic cancer cell line PC-3. In contrast, lysosomal acid phosphatase (LAP) mRNA was detected in both of these human prostatic cancer cell lines. Our findings indicate a high specificity for the PAP gene in prostatic tissue. The mean abundance for the PAPmRNA expression was 0.26 for prostatic carcinoma samples (n = 11) and 0.46 for BPH samples (n = 8) according to slot-blot analysis. The differences observed between the different categories of prostatic tissue in PAPmRNA abundances call for additional studies on regulation of its expression.     

Prostate-specific antigen in prostate cancer

Prostate-specific antigen (PA) has been evaluated clinically as a tumor marker of prostate cancer with the use of enzyme immunoassay (EIA). For serodetection of prostate cancer, PA was assayed in a total of 1,109 sera. From mean +/- 3 S.D. of normal controls, upper cut-off values in males were decided as 2.5 and 1.2 ng/ml in Americans and Japanese, respectively. Serum PA values in prostate cancer patients were positive in 78% of Americans and 62% of Japanese. However, in benign prostatic hypertrophy (BPH) cases, a high false positive rate of 41% was observed in Americans. Simultaneous assays of serum PA and PAP showed high sensitivity and specificity in the detection of prostate cancer. This antigen could be used, as well as PAP, for monitoring prostate cancer patients. Furthermore, serum PA levels prior to treatment may express to some degree the malignant potential of the cancer. These results suggest that PA may be useful as a tumor marker of prostate cancer.     

Are plasma insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) useful markers of prostate cancer?

Increased concentrations of insulin-like growth factor I (IGF-I) and decreased insulin-like growth factor binding protein 3 (IGFBP-3) in serum have been proposed as markers of prostate cancer (CaP). The evidence for this, however, is contradictory. We assayed serum for IGF-I, IGFBP-3 and prostate-specific antigen (PSA) in patients with CaP and benign prostatic hyperplasia (BPH) and in healthy controls (HC). The mean +/- SD concentration of IGF-I in CaP (98.3 +/- 39.3 ng/mL; n = 15) was lower than in BPH (119 +/- 31.1 ng/mL; n=24) and HC (119 +/- 36.1 ng/mL; n=46), but the differences between the three groups were not statistically significant (p > 0.05). The mean IGFBP-3 concentrations in CaP (2691 +/- 1105 ng/mL; n = 16; p = 0.029) and BPH (2618 +/- 816 ng/mL; n = 26; p = 0.006) patients were significantly lower than that of the HC (3119 +/- 618 ng/mL; n=59), but the difference between the two groups of patients was not significant (p > 0.05). PSA concentrations in CaP (median = 80.8 ng/mL; n = 25) were significantly higher than those in BPH (median = 8.6 ng/mL; n = 39) (p < 0.001). Ninety-six percent of CaP and 72% of BPH patients had PSA concentrations >4.0 ng/mL; the proportions of patients with concentrations exceeding 20 ng/mL were 76% and 10%, respectively. We conclude that IGF-I and IGFBP-3 are inferior to PSA for CaP detection.     

PSA相关指标对前列腺癌诊断价值的评价及比较研究

目的:探讨血清总PSA(TPSA)、F/TPSA和PSA密度(PSAD)在前列腺癌(PCa)诊断中的价值,寻找更准确的前列腺癌诊断指标。方法:采用化学发光免疫分析法检测前列腺癌患者(60例)和前列腺增生患者(240例)的血清PSA水平,通过B超测定患者前列腺的体积,计算PSAD,运用ROC曲线评价和比较血清总PSA(TPSA)、F/TPSA和PSAD诊断前列腺癌的准确性和特异性。结果:(1)前列腺癌患者TPSA和PSAD值均明显高于前列腺增生患者(P0.01),F/TPSA明显低于前列腺增生患者(P0.01);(2)TPSA阈值定为4 ng/ml时,诊断前列腺癌的敏感性、特异性分别为56.23%、80.10%。F/TPSA阈值定为0.15时,诊断前列腺癌的敏感性、特异性分别为88.10%、69.10%,PSAD阈值定为0.20时,诊断前列腺癌的敏感性、特异性分别为88.60%、88.30%。结论:TPSA、F/TPSA和PSAD在前列腺癌诊断中均有一定的价值,且PSAD诊断前列腺癌的敏感性、特异性优于TPSA、F/TPSA,是诊断前列腺癌更为理想的指标。     

Immunocytochemical detection of prostate-specific antigen (PSA) in skin adnexal and breast tissues and tumors

Prostate Specific Antigen (PSA) is regarded as a specific marker of prostatic epithelium and has never been detected by immunocytochemistry in extra-prostatic tissues. The casual finding of a strong positivity for polyclonal antisera to PSA in a sweat gland carcinoma prompted a study on a series of skin adnexial and breast specimens (normal and neoplastic). Normal axillary and perineal apocrine sweat glands, some apocrine foci in fibrocystic breast disease and two sweat gland and two breast apocrine carcinomas were stained by several PSA antisera; a recently introduced monoclonal to PSA, however, was unreactive. These observations cast doubt on the specificity of PSA for prostatic epithelium, especially when polyclonal antisera are employed. Immunocytochemical reactions obtained with PSA, in the investigation of skin, lesions must be interpreted with caution and confirmed if necessary with monoclonals to PSA and with PAP.     

Trends in Prostate Specific Antigen (PSA) testing and prostate cancer incidence and mortality in Australia: A critical analysis

BackgroundPopulation trends in PSA testing and prostate cancer incidence do not perfectly correspond. We aimed to better understand relationships between trends in PSA testing, prostate cancer incidence and mortality in Australia and factors that influence them.MethodsWe calculated and described standardised time trends in PSA tests, prostate biopsies, treatment of benign prostatic hypertrophy (BPH) and prostate cancer incidence and mortality in Australia in men aged 45–74, 75–84, and 85 + years.ResultsPSA testing increased from its introduction in 1989 to a peak in 2008 before declining in men aged 45–84 years. Prostate biopsies and cancer incidence fell from 1995 to 2000 in parallel with decrease in trans-urethral resections of the prostate (TURP) and, latterly, changes in pharmaceutical management of BPH. After 2000, changes in biopsies and incidence paralleled changes in PSA screening in men 45–84 years, while in men ≥85 years biopsy rates stabilised, and incidence fell. Prostate cancer mortality in men aged 45–74 years remained low throughout. Mortality in men 75–84 years gradually increased until mid 1990s, then gradually decreased. Mortality in men ≥ 85 years increased until mid 1990s, then stabilised.ConclusionAge specific prostate cancer incidence largely mirrors PSA testing rates. Most deviation from this pattern may be explained by less use of TURP in management of BPH and consequent less incidental cancer detection in TURP tissue specimens. Mortality from prostate cancer initially rose and then fell below what it was when PSA testing began. Its initial rise and fall may be explained by a possible initial tendency to over-attribute deaths of uncertain cause in older men with a diagnosis of prostate cancer to prostate cancer. Decreases in mortality rates were many fold smaller than the increases in incidence, suggesting substantial overdiagnosis of prostate cancer after introduction of PSA testing.     

Estrogen and G protein-coupled estrogen receptor accelerate the progression of benign prostatic hyperplasia by inducing prostatic fibrosis

Benign prostatic hyperplasia (BPH) is the most common and progressive urological disease in elderly men worldwide. Epidemiological studies have suggested that the speed of disease progression varies among individuals, while the pathophysiological mechanisms of accelerated clinical progression in some BPH patients remain to be elucidated. In this study, we defined patients with BPH as belonging to the accelerated progressive group (transurethral resection of the prostate [TURP] surgery at ≤50 years old), normal-speed progressive group (TURP surgery at ≥70 years old), or non-progressive group (age ≤50 years old without BPH-related surgery). We enrolled prostate specimens from the three groups of patients and compared these tissues to determine the histopathological characteristics and molecular mechanisms underlying BPH patients with accelerated progression. We found that the main histopathological characteristics of accelerated progressive BPH tissues were increased stromal components and prostatic fibrosis, which were accompanied by higher myofibroblast accumulation and collagen deposition. Mechanism dissection demonstrated that these accelerated progressive BPH tissues have higher expression of the CYP19 and G protein-coupled estrogen receptor (GPER) with higher estrogen biosynthesis. Estrogen functions via GPER/Gαi signaling to modulate the EGFR/ERK and HIF-1α/TGF-β1 signaling to increase prostatic stromal cell proliferation and prostatic stromal fibrosis. The increased stromal components and prostatic fibrosis may accelerate the clinical progression of BPH. Targeting this newly identified CYP19/estrogen/GPER/Gαi signaling axis may facilitate the development of novel personalized therapeutics to better suppress the progression of BPH.Subject terms: Urogenital reproductive disorders, Prostatic diseases, Preclinical research, Endocrine reproductive disorders     

Long-Term Experience with 5-alpha-Reductase Inhibitors

Finasteride, a 5-alpha-reductase inhibitor, dramatically suppresses the production of dihydrotestosterone in men; thus, attention has turned to this agent for the treatment of benign prostatic hyperplasia (BPH). A number of randomized clinical trials have studied finasteride's effects on prostate size, BPH symptoms, flow rate, and prostate-specific antigen (PSA) level. Although the decrease in symptoms with finasteride therapy has been modest compared with more invasive treatments, its use has resulted in sustained reductions in prostatic volume and PSA level with minimal adverse effects. Fewer surgeries for BPH, as well as a decreased incidence of acute urinary retention, have also been seen with finasteride therapy. More research is needed to maximize the effectiveness of such medical therapy for BPH.     

Unoccupied prolactin binding components of the benign and malignant human prostate in a subclinical and clinical procedure

Optimal conditions for the quantitation of free prolactin binding components of human prostatic tissue obtained by TURP were studied by applying γ receptor assay. The radioligand used was ¹²⁵I-prolactin. Significantly greater heat stability of the prostate membrane prolactin binding sites, when compared to that of androgen cytoplasmic receptors, was confirmed. The saturability and specificity of the prolactin binding components was demonstrated by the results of both Scatchard plot analysis and displacement studies. Free prolactin receptors were found in none of the poorly differentiated (G3) prostatic tumors examined, and only in 62.5% of medium differentiated (G2) prostatic malignancies. The majority of tissue specimens coming from patients with either BPH or well differentiated prostatic tumor (G1) contain measurable amounts of free prolactin membrane binding components. In the present study we report also the case in which the change in tumor differentiation toward a higher grade (G2 to G1, provoked by the successful chemohormonal treatment) is accompanied with the appearance of previously absent free prolactin binding components. In histologically proven BPH tissue specimens free prolactin receptor negative status has been found in most patients with a slight increase in serum PAP values, while receptor rich status was detected in the majority of those with elevated PSA concentrations. We believe therefore that the prolactin receptor values, when used as part of the multivariable analysis, may participate in further delineation of the role of prolactin in the development of prostate cancer, but may also play a role in a subclinical prediction related to the conversion of either an adenoma or a latent adenocarcinoma to the clinically manifest prostatic malignancy.