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.     

Serum prostate-specific antigen determination in prostatic carcinoma

Prostate-specific antigen (PSA) is a tissue-specific glycoprotein identified by Wang in 1979. It is synthesized in the prostate independently of prostatic acid phosphatase (PAP). A total of 199 subjects were divided into four groups: controls aged less than 50 years, controls aged more than 50 years, patients with benign prostatic hyperplasia (BPH) and patients with prostatic carcinoma. PSA cut-off value was set at 10 ng/ml (mean for the BPH group plus 2 SD). With this cut-off value PSA could not be used as an early predictor of prostatic carcinoma. The association of PSA and PAP in prostatic cancer increases the number of patients with positive biological markers.     

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.     

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.     

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.     

Analysis of relations between serum levels of epitestosterone, estradiol, testosterone, IGF-1 and prostatic specific antigen in men with benign prostatic hyperplasia and carcinoma of the prostate

Epitestosterone competes with testosterone for androgen receptors and inhibits several enzymes of steroidogenesis. Insulin-like growth factors (IGFs) stimulate the growth of prostate cells and directly activate androgen receptors in prostatic tumor cell lines. The prostate-specific antigen (PSA) decreases the affinity of IGF-binding protein-3. The samples were collected from 71 patients suffering from various diseases of the prostate (56 patients without prostate cancer but with benign prostatic hyperplasia and 15 patients with prostate cancer). Correlations between age and IGF-1 (r = -0.281, p<0.05), age and serum epitestosterone (r = -0.261, p<0.05), estradiol and testosterone (r = 0.367, p<0.01), and between estradiol and epitestosterone (r = -0.414, p<0.001) were found. After age adjustment, IGF-I correlated with epitestosterone (r = -0.277, p<0.05). The age correlated positively with PSA (r = 0.286, p<0.05) and negatively with IGF-1 (r = -0.377, p<0.01) in partial correlations. PSA levels were higher in patients with prostate cancer (p<0.00001). Epitestosterone, which is negatively correlating with estradiol and IGF-1, may modulate the development of prostate diseases.     

Prostate cancer vs hyperplasia: relationships with prostatic and adipose tissue fatty acid composition

The objective of the present study was to study whether adipose tissue and prostatic tissue fatty acid composition differentiates between prostate cancer and benign hyperplasia patients. In addition, the present investigation aimed at exploring the extent to which prostatic tissue fatty acid composition differentiates between prostate-confined cancer and extraprostatic disease including possible metastasis. The subjects were 71 male patients from the island of Crete. Half the patients (n=35) had been diagnosed with benign hyperplasia of the prostate, half with prostatic malignancy (n=36). Patients were examined at the outpatient clinic of the urology unit, University Hospital, Medical School, University of Crete. Relative to benign hyperplasia patients, cancer patients had elevated adipose tissue saturated and reduced monounsaturated fatty acid levels. Cancer patients had reduced prostate tissue stearic to oleic acid ratios and stearic acid levels as opposed to hyperplasia patients. The most pronounced difference between cancer patients and hyperplasia patients was a 3-fold elevated prostatic palmitoleic acid in the former group. Relative to benign hyperplasia patients, cancer patients had reduced prostate tissue arachidonic and docosahexaenoic acid levels. Finally, there was a significantly reduced omega-3/omega-6 polyunsaturated fatty acid ratio in the prostate cancer patient as opposed to the benign hyperplasia group. The pronounced elevations in prostatic tissue palmitoleic acid in cancer patients highlight a possible role of this fatty acid in neoplastic processes. The decreased arachidonic acid levels in cancer patients possibly stem from enhanced metabolism of arachidonic acid via lipoxygenase and cyclooxygenase pathways, and the formation of derivatives such as 5-HETE, 15-HETE, 12(S)-HETE and PGE(2).     

Comparative analysis of prostatic acid phosphatase and prostate-specific antigen mRNA levels in hyperplastic prostate stimulated with steroid hormones and growth factors

Prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) are the markers of human prostatic gland. However, it is still not completely understood if and how, steroid hormones and growth factors affect their expression and metabolism in the respect to the major pathologies of the gland. Appropriate studies were carried out on histopathologically diagnosed benign prostatic hyperplasia--BPH (n = 42) using tissue slices and cells derived from them. They were incubated with steroid hormones: 5-alpha-dihydrotestosterone (DHT), estradiol (E) and growth factors: epidermal growth factor (EGF), basic fibroblastic growth factor (bFGF) under culture conditions for up to 24 hours. P-labelled specific oligonucleotide probes were used to analyze total RNA isolated from each sample for the presence of PAP and PSA mRNAs. DHT, E, bFGF, EGF or both DHT + bFGF and DHT + EGF increased PAP and PSA mRNA levels in a time- and dose-dependent manner. The highest and statistically significant increase (P < 0.001) for PAP mRNA was observed when DHT + bFGF were present in the medium while for PSA mRNA if DHT + EGF were added to the medium. Slow but constant decrease of PAP and PSA mRNA levels was observed in the absence of each of these factors in the incubation medium. The results suggest that early expression of PSA and PAP genes and/or their mRNA stability strongly depend on DHT while differ in their response to EGF and bFGF.     

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.     

Combination of Autoantibody Signature with PSA Level Enables a Highly Accurate Blood-Based Differentiation of Prostate Cancer Patients from Patients with Benign Prostatic Hyperplasia

Although an increased level of the prostate-specific antigen can be an indication for prostate cancer, other reasons often lead to a high rate of false positive results. Therefore, an additional serological screening of autoantibodies in patients’ sera could improve the detection of prostate cancer. We performed protein macroarray screening with sera from 49 prostate cancer patients, 70 patients with benign prostatic hyperplasia and 28 healthy controls and compared the autoimmune response in those groups. We were able to distinguish prostate cancer patients from normal controls with an accuracy of 83.2%, patients with benign prostatic hyperplasia from normal controls with an accuracy of 86.0% and prostate cancer patients from patients with benign prostatic hyperplasia with an accuracy of 70.3%. Combining seroreactivity pattern with a PSA level of higher than 4.0 ng/ml this classification could be improved to an accuracy of 84.1%. For selected proteins we were able to confirm the differential expression by using luminex on 84 samples. We provide a minimally invasive serological method to reduce false positive results in detection of prostate cancer and according to PSA screening to distinguish men with prostate cancer from men with benign prostatic hyperplasia.     

Expression of prostate specific membrane antigen (PSMA) in prostatic adenocarcinoma and prostatic intraepithelial neoplasia

The prostatic membrane antigen (PSMA) is a protein that is expressed in the prostatic epithelium. We studied the expression of PSMA in a series of 55 patients with different stages of prostate cancer and we compared the PSMA staining in prostate cancer cells, in high-grade prostatic intraepithelial neoplasia (PIN) and in histologically benign prostatic epithelium for the same specimen. For this purpose archival paraffin-embedded specimens were studied by immunohistochemistry with a monoclonal antibody 7E11-C5.3 against PSMA using the streptavidin-biotin method. The mean percentage of PSMA immunoreactivity was 56.67% in prostate cancer (CaP) cells, and 48.6% in PIN cells, which was significantly higher than benign-appearing prostatic epithelium (5.72%) (for each pair, p<0.001). PSMA expression was greater in CaP with a higher Gleason score (p=0.01), but no relationship was found with serum PSA value. We conclude that PSMA overexpression is detected in high-grade PIN and is associated with a higher Gleason score of prostate cancer. It is a potential marker for studying carcinogenesis and progression of prostate cancer.     

血清前列腺特异性抗原与前列腺增生的相关性研究

目的:探讨前列腺增生患者年龄,前列腺体积以及BMI与血清前列腺特异性抗原(PSA)之间的关系。方法:对224例前列腺增生患者的年龄,前列腺体积以BMI与PSA的相关性进行Spearman相关性分析。结果:224例前列腺增生患者有25%的患者PSA水平高于正常,并且年龄,前列腺体积与血清PSA存在明显的正相关:(r=0.672.P<0.01,r=0.785.P<0.01),而血清PSA与BMI指数存在明显的负相关:(r=-0.873,P<0.01)。结论:前列腺增生患者的血清PSA值随患者年龄增长和体积增大而增加,对于PSA轻度升高的前列腺增生患者,要考率到体重因素对结果的影响。     

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。     

磁共振成像联合血清前列腺特异抗原、上皮钙黏蛋白、早期前列腺癌抗原-2诊断前列腺癌的临床价值探讨

摘要 目的：探究磁共振成像（MRI）联合血清前列腺特异抗原（PSA）、上皮钙黏蛋白（sE-cadherin）、早期前列腺癌抗原-2（EPCA-2）诊断前列腺癌的临床价值。方法：选取潍坊市人民医院2020年1月-2021年7月期间经病理证实的50例前列腺癌患者（前列腺组）以及50例前列腺增生患者（前列腺增生组）展开回顾性研究。100例研究对象均完善了MRI检查并测定血清PSA、EPCA-2、sE-cadherin水平,分析两组患者的MRI影像学特征,比较两组患者的PSA、EPCA-2、sE-cadherin水平以及各项检查方法的诊断准确性差异。结果：前列腺癌的MRI影像学特征为病灶主要位于外周带,外周带T2W呈低信号,病变侵及包膜、膀胱及周围组织具有T1加权消失或者不对称,具有信号异常、肌肉增厚的表现,盆腔淋巴结转移具有淋巴结部分融合或增大表现;前列腺增生的MRI影像学特征为边界清晰、包膜完整并且中央带增生、不均匀信号结节;前列腺癌、前列腺增生均存在不同程度的前列腺体积增大。相比于前列腺增生组,前列腺癌组患者的PSA、sE-cadherin、EPCA-2水平明显更高（P<0.05）。MRI、PSA、sE-cadherin、EPCA-2四项联合鉴别前列腺癌、前列腺增生的诊断符合率为96.00%,明显高于四项单独诊断的88.00%、79%、81%、82%（P<0.05）。结论：MRI联合PSA、sE-cadherin、EPCA-2鉴别诊断前列腺癌的准确性较高,具有作为临床前列腺癌早期诊断指导方案的潜力。     

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.     

血清前列腺特异性抗原与前列腺增生的相关性研究

目的：探讨前列腺增生患者年龄,前列腺体积以及BMI与血清前列腺特异性抗原（PSA）之间的关系。方法：对224例前列腺增生患者的年龄,前列腺体积以BMI与PSA的相关性进行Spearman相关性分析。结果：224例前列腺增生患者有25％的患者PSA水平高于正常,并且年龄,前列腺体积与血清PSA存在明显的正相关：（r=0．672．P〈0．01,r=0．785．P〈0．01）,而血清PSA与BMI指数存在明显的负相关：（r=-0．873,P〈0．01）。结论：前列腺增生患者的血清PSA值随患者年龄增长和体积增大而增加,对于PSA轻度升高的前列腺增生患者,要考率到体重因素对结果的影响。     

Hormonal modulation of biosynthesis of prostatic specific antigen, prostate specific acid phosphatase and prostatic inhibin peptide.

Hormonal modulation of in vitro biosynthesis of three prostatic secretory proteins, prostate specific acid phosphatase (PSAP), prostate specific antigen (PSA) and prostatic inhibin peptide (PIP) by human benign hyperplasia (BPH) tissue was studied. LH and inhibins caused increase in the synthesis of all three proteins whereas FSH enhanced the synthesis of PIP and PSA only but decreased PSAP synthesis. Prolactin and thyroid releasing hormone decreased synthesis of PIP and PSAP. However, PSA synthesis was enhanced by TRH and was decreased by prolactin. Estradiol caused significant increase in PSA and PSAP but no discernible changes in PIP synthesis were noticed. Testosterone caused an increase in PIP, PSA and PSAP. These data indicate that biosynthesis of PIP, PSA and PSAP by BPH tissue is under multihormonal regulation.     

Nuclear volume estimates in prostatic atypical adenomatous hyperplasia

OBJECTIVE: To investigate nuclear volume estimates by the point-sampled intercepts method in atypical adenomatous hyperplasia (AAH) as compared with nodular hyperplasia and well-differentiated prostatic adenocarcinoma. STUDY DESIGN: The study group consisted of 27 formalin-fixed, paraffin-embedded, whole-mounted radical prostatectomy specimens that contained foci of nodular hyperplasia, atypical adenomatous hyperplasia and well-differentiated adenocarcinoma (Gleason pattern 1 and 2). Representative sections were selected for stereologic estimation of volume-weighted mean nuclear volume by the point-sampled intercepts method. On each focus, an average of five fields of vision were systematically chosen. RESULTS: The quantitative results indicate an increase in nuclear volume from nodular hyperplasia (209 +/- 65 micron 3) to AAH (237 +/- 85 micron 3) and prostate adenocarcinoma (436 +/- 106 micron 3). Significant differences were found (F = 39.0, P < .001) with two group comparisons (Scheffe's procedure) between prostate cancer and AAH (P < .001) or nodular hyperplasia (P < .001). The difference between AAH and benign hyperplasia was not signifcant. CONCLUSION: The results indicate that three-dimensional estimates of the nuclear size discriminate AAH and nodular hyperplasia from well-differentiated prostate adenocarcinoma. These findings suggest that AAH is probably a histologic variant of benign prostatic hyperplasia the exact relationship of which to prostatic adenocarcinoma remains to be determined.     

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.     

The application of the RT-PCR method for the staging of the prostate cancer progression

Molecular biology seems to bring more convincing markers for the detection of prostate cancer as well as the development of metastases than immunohistochemistry. The main goal of present work was to detect the expression of prostate specific antigen (PSA) and prostate-specific membrane antigen (PSM) genes in the micrometastases by the RT-PCR to assess the progression of prostate cancer. We analyzed 50 patients: 28 patients with clinically localized or locally advanced prostate cancer who underwent radical prostatectomy, 7 patients with clinically proven metastases, 8 patients with benign prostatic hyperplasia, and 7 healthy young men. The results of RT-PCR in the first group of 28 patients varied, however, they were in good correlation with the health status of the patients. Positive results of PSA and notably for PSM were good predictors of beginning metastasing process. Seven patients with metastatic disease had positive RT-PCR results both for PSA and PSM. All of the patients with benign prostatic hyperplasia and healthy young men had negative RT-PCR results for PSA and PSM. The study showed that positive RT-PCR results for PSA and especially for PSM correlated well with the progression of the disease and negative results reflected good health status of the patients.