Serum insulin-like growth factor-1 is not a useful marker of prostate cancer.

OBJECTIVE: To determine whether the use of serum insulin-like growth factor 1 (IGF-1) levels is more efficient than serum prostate specific antigen (PSA) levels in predicting prostate cancer in patients undergoing prostatic biopsy. PATIENTS AND METHODS: The study included 94 consecutive patients who required transrectal ultrasonography (TRUS)-guided biopsies of their prostate and who had blood samples taken before their biopsies. These samples were then analysed for IGF-1 and PSA concentrations. Six prostatic biopsies were taken from each patient; they were assessed and a diagnosis made of prostate cancer or no malignancy. RESULTS: Thirty-seven patients were found to have prostate cancer and 57 had no evidence of malignancy. There was no statistical difference in serum IGF-1 levels between these groups. The PSA level and age of the patients differed significantly between the groups (both P<0.001). There was no correlation between IGF-1 and PSA levels, and even when the age difference in the groups was considered, there was still no significant relationship between IGF-1 levels and the incidence of prostate cancer. In patients with a PSA level of 4-20 microg/L there was no statistically significant difference in IGF-1 levels between the groups. CONCLUSION: Serum IGF-1 as a tumour marker does not help to predict patients with prostate cancer. PSA level and even age were better predictors of the presence of prostate cancer than were serum IGF-1 levels.     

Clinical implications of introducing a new PSA assay

BACKGROUND: A number of different prostate-specific antigen (PSA) assays are in common use. There has been little consideration of the possible clinical implications of interassay variation. The availability of two assays in the same laboratory provided an opportunity to audit the clinical implications of the interassay variation in PSA levels. METHODS: The same serum samples from patients with prostate cancer on follow-up were analyzed for PSA by the Abbott AxSYM assay and by the Abbott ARCHITECT assays. To assess within-patient reproducibility of the interassay variation, repeat analysis of PSA by both assays was conducted in a second sample obtained at least 1 month after the first. RESULTS: Samples from 156 cases were analyzed. The mean ratio of serum PSA values by the two assays (AxSYM assay/ARCHITECT assay) was 0.89 (range 0.5-2.27). The interassay coefficient of variation was 20%. In a subgroup of 50 cases with repeat samples available, the correlation coefficient, r, of the interassay variation in PSA between the first and second samples was 0.441. CONCLUSIONS: Interassay variation in serum PSA is clinically significant, both between patients and on repeated measurement within the same patient. Clinicians should be aware that simple correction factors may not accurately control for variation between PSA assays. Ideally, patients on follow-up for prostate cancer should be monitored using a single PSA assay.     

Value of prostate-specific antigen measurements with newly developed enzyme immunoassay (MARKIT-M PA)]

Serum prostate-specific antigen (PSA) levels in patients with prostate cancer and benign prostate hypertrophy (BPH) were investigated with a newly developed enzyme immunoassay (MARKIT-M PA, Dainippon Pharmaceutical Co. Ltd., Osaka, Japan). Sensitivity of the assay system is 0.5 ng/ml and the detection range is 0.5-100 ng/ml. There was a high linear correlation (r = 0.987) between the assay and MARKIT-F PA, and values obtained with the assay were almost equal to those yielded by MARKIT-F PA assay. Using the BPH group as a negative control, the upper cut-off value in BPH patients was determined to be 3.6 ng/ml. Of the 48 patients with untreated prostate cancer, 77% was detectable by means of MARKIT-M PA assay. Using the BPH group as a negative control, specificity and efficiency were 93% and 86%, respectively. In another group of 27 BPH patients whose blood samples were taken immediately after digital prostatic examination, PSA was elevated in 15%. During follow-up of prostate cancer patients, PSA was elevated in 82% at the time of clinically detectable progression. In 15 patients whose disease was clinically well controlled, all levels of PSA were observed to be negative. These findings suggests that detection of serum PSA with this assay is of great use both in the diagnosis and monitoring of prostate cancer patients.     

Evidence for the existence of an organ specific, androgen-independent pathway of progression in patients with metastatic prostate cancer

Ample clinical and preclinical data support the central role of bone-epithelial interaction in the progression of prostate cancer. The clinical progression of prostate cancer has been partially attributed to a cascade of interactions between the cancer compartment and microenvironment compartments. The expression of prostate specific antigen (PSA) parallels the activity of the epithelial compartment of prostate cancer. However, the clinical study of the bone-epithelial interaction has been limited by the lack of accessible relevant human tissue for study. This study was designed (1) to assess the value of human bone marrow as a source of tissue to study the bone-epithelial interaction and (2) to determine whether bone marrow supernatant regulates the expression of PSA in a human prostate cancer cell line (LNCaP) in vitro. The acellular bone marrow supernatant derived from patients with prostate cancer with different degrees of tumor spread, hormonal status, and histology were assayed for their ability to induce PSA expression in a human LNCaP. The bone marrow supernatants were derived from 53 patients with prostate cancer (49 with adenocarcinoma and 4 with small cell carcinoma) and eight control patients, who had cancers in other sites. In addition, the match serum specimens derived from 25 of the study patients also had been assayed for its PSA inductivity. In addition to the comparison with "static" serum and BM concentration of PSA, the rate of significant PSA induction by clinical stage and hormonal status was assessed. Patients with androgen-independent disease had the highest rate of PSA-inducing ability. Only two patients (8%) had weak PSA-inducing ability from their serum (both with high volume disease) and none of the bone marrow supernatants derived from patients without prostate cancer or small cell carcinoma had inducing ability. No correlation between the static BM or serum PSA concentrations and the inducing ability was seen. These results indicate that PSA expression can be regulated by androgen-independent factors. The bone marrow supernatant of patients with prostate cancer has unique properties and is a valuable source of tissue for clinical study of the progression of prostate cancer. These preliminary data suggest that induction of PSA by bone marrow supernatant should be studied for its clinical utility as an assay for the interaction between the epithelial and bone compartments, and it supports the existence of androgen-independent pathways of PSA regulation by the bone marrow supernatant of patients with advanced prostate cancer. If confirmed, these findings would support the use of bone marrow supernatant to study the osseous specific progression of prostate cancer.     

STABILITY OF FREE AND TOTAL PROSTATE SPECIFIC ANTIGEN IN SERUM FROM PATIENTS WITH PROSTATE CARCINOMA AND BENIGN HYPERPLASIA

Purpose

Instability of prostate specific antigen (PSA) in serum might complicate the interpretation of the free-to-total PSA ratio. We studied the in vitro stability of free PSA and total PSA in serum of patients with prostate cancer or benign prostate hyperplasia (BPH), and of elderly man without known prostate disease. Furthermore, we investigated conditions to stabilize the in vitro values in serum.

Materials and Methods

The effects of storage at 4C on free and total PSA were investigated in serum of 32 men with prostate cancer, 25 with BPH and 29 older than 70 years. All had total PSA less than 25 micro g./l. The influence of total PSA levels on in vitro changes in free-total PSA was studied in serum of 39 other prostate cancer patients (total PSA 1.7 to 298 micro g./l.). Stabilization studies were performed in yet another series of samples from 54 prostate cancer patients (total PSA 1.3 to 238 micro g./l.) by adjustment of serum pH to 5.5 before storage. Free and total PSA was measured by a commercial immunofluorometric assay, as well as by in-house immunofluorometric assays. Statistical analyses of the results were performed by analysis of variance with repeated measures.

Results

We found no difference between the results obtained by the 2 assay systems. After 7 days at 4C there was a slight decrease in total PSA in sera of prostate cancer patients, BPH patients and men older than 70 years. A decrease in mean free PSA values occurred in all groups (21.3, 15.7 and 14.6%, respectively). The decrease of free PSA with time was significant (p <0.0001) in all groups but there was no significant difference among the groups (p = 0.16). The concomitant decrease in free-to-total PSA ratio was significant in all groups (p <0.0001). This change was group dependent (p = 0.003), with the largest decrease in the prostate cancer group. Large interindividual differences were observed. Storage at 4C for 7 days of sera of 39 patients with localized and disseminated prostate cancer (total PSA 1.7 to 298 micro g./l.) gave a more pronounced decrease in free PSA than in total PSA. Adjustment of serum pH to 5.5 had a stabilizing effect on free PSA and on the free-to-total PSA ratio, giving a significantly smaller change in both values (p <0.0001).

Conclusions

In vitro instability of free PSA in serum and large interindividual differences should be considered when using the ratio of free-to-total PSA in evaluation of patients with suspected prostate cancer. Serum samples should be stored frozen if not analyzed immediately or acidified to pH 5.5. Interpretation of data from determination of free-to-total PSA ratio should be done with caution if the sampling and storage conditions are not known.     

Correlation of histological inflammation in needle biopsy specimens with serum prostate- specific antigen levels in men with negative biopsy for prostate cancer

OBJECTIVES: To reveal the possible contribution of histological inflammation within the prostate to the abnormal elevation of serum prostate-specific antigen (PSA) levels in patients with needle biopsy negative for prostate cancer. METHODS: We reviewed negative needle biopsy specimens obtained in 93 patients. The degree of acute and chronic inflammation as evaluated histologically was compared with serum PSA levels in conjunction with age and prostate volume. RESULTS: Both age (P <0.01) and prostate volume (P <0.0001) correlated significantly with serum PSA levels and were significantly greater in patients with abnormal serum PSA levels (greater than 4.0 ng/mL) than in those with normal serum PSA levels (4.0 ng/mL or less) (P <0.01). The presence of histological inflammation within the prostate also correlated significantly with serum PSA levels. Multiple regression analysis demonstrated prostate volume to be the only independent determinant of serum PSA levels (P <0.01). In patients with a prostate volume larger than 25 mL, only prostate volume correlated significantly with serum PSA levels (P <0. 05). On the other hand, the degree of acute inflammation as represented by polymorphonuclear leukocyte infiltration was the only parameter correlating significantly with serum PSA levels (P <0.05) in patients with a prostate volume smaller than 25 mL. CONCLUSIONS: Histologically defined acute inflammation within the prostate is a significant contributor to elevated serum PSA levels, especially in patients with small prostates. In the assessment of needle biopsy results negative for prostate cancer, it might be helpful to evaluate the degree of histological inflammation, especially in terms of the necessity of subsequent repeated biopsies.     

Daily variability in human serum prostate-specific antigen and prostatic acid phosphatase: a comparative evaluation

The daily variation of serum levels of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) was investigated simultaneously in 10 patients with osseous metastatic prostatic cancer, 10 patients with benign prostatic hyperplasia, and 10 volunteers without prostatic disease. Duplicate serum samples were obtained from all patients on the same day at 8 AM, 12 PM, 4 PM, and 8 PM. Statistical analysis (two-factor analysis of variance comparing time period to disease group) of the mean PSA and PAP levels at the four sampling times on all patient groups demonstrated no evidence of circadian rhythmic variation or any other distinct pattern for the observed sample times. Overall, the variability in PSA levels was significantly less than that observed for PAP. There was no significant difference in mean percent variation between patient groups (cancer, benign, and normal prostate glands) for both the PSA and PAP assays. Our data reveal that serum PSA measurements fluctuate unpredictably over the course of a day in patients with and without prostatic disease, but to a lesser extent than that seen for serum PAP values. These findings illustrate the potential inaccuracy of single determinations of serum PAP or PSA levels for monitoring disease recurrence and treatment response in patients with prostate cancer.     

Concentration of enzymatically active prostate-specific antigen (PSA) in the extracellular fluid of primary human prostate cancers and human prostate cancer xenograft models

BACKGROUND: Prostate-specific antigen (PSA) targeted prodrugs are under development in our laboratory. Concentrations of total PSA and enzymatically active PSA produced by various human prostate cancer xenograft models have not been well characterized. METHODS: The concentration of PSA secreted into the extracellular fluid (ECF) in normal human prostate tissue, primary prostate cancers obtained directly from patients, and serially passageable human prostate cancer xenografts (PC-82, LNCaP, LAPC-4) were determined using Tandem assays. Percent enzymatically active PSA in the ECF and in conditioned media was also determined using a previously validated assay employing a monoclonal antibody to the PSA catalytic site. In addition, the concentration and activity of PSA within sera from men with and without prostate cancer, as well as from tumor-bearing animals, was likewise assayed. RESULTS: Normal human prostate tissue and primary human prostate cancers have high concentrations of PSA in the ECF (i.e., 1600-2100 nM). The majority of this PSA is enzymatically active (i.e., 80-90%). Human PC-82 prostate cancer xenografts also have high concentrations of PSA in the ECF (624 +/- 360 nM), and the majority of this PSA is also enzymatically active (i.e., 66 +/- 4%). In contrast, much lower concentrations of PSA are found in the ECF from LNCaP (45 +/- 9 nM) and LAPC-4 (7.3 +/- 0.6 nM). Only a small portion of the total PSA isolated from DHT-containing, serum-free, conditioned media from these cell lines is enzymatically active (i.e., approximately 18%). While PSA was detected in all serum samples regardless of the type of host, no enzymatically active PSA was detected in any of these serum samples. CONCLUSIONS: Prostate cancers obtained directly from patients produce and secrete large amounts of PSA, the majority of which is highly enzymatically active. In contrast, while PSA was detected in the sera, none of this PSA was enzymatically active. This is also the case for the human PC-82 prostate cancer xenografts. In contrast, LNCaP and LAPC-4 human prostate cancer xenograft models secrete approximately 70-300-fold less PSA in the ECF than prostate cancers from patients and the majority of this PSA is enzymatically inactive. Also, the serum from these animals had detectable PSA, but none of this PSA was enzymatically active. Thus, these latter two prostate cancer models define the least and the PC-82, the most, optimized xenograft model for screening PSA targeted prodrugs.     

Rapid elimination by glomerular filtration of free prostate specific antigen and human kallikrein 2 after renal transplantation

PURPOSE: The low molecular mass and short half-life of free (f) prostate specific antigen (PSA) implies elimination from blood by glomerular filtration. In addition, patients with terminal renal failure have increased fPSA in serum but there have been sparse data reported on the rates and pathways of elimination of PSA complexes and human kallikrein 2 (hK2). We studied glomerular filtration dependent elimination of fPSA and hK2 in patients with renal insufficiency undergoing successful renal transplantation. MATERIALS AND METHODS: We studied 14 patients with immediate onset of renal function after renal transplantation. Blood samples were obtained before and at regular intervals up to 160 hours after transplanted kidney reperfusion. Measurements of fPSA, total PSA and hK2 were performed with immunofluorometric assays and complexed PSA was determined by a chemiluminiscence assay. Glomerular filtration rates were monitored by analyzing serum creatinine and cystatin C. NONMEM, a multivariate pharmacokinetic approach, was used to determine the elimination rates of fPSA and hK2 after renal transplantation. RESULTS: Serum fPSA and hK2 but not PSA complexes, decreased rapidly after renal transplantation. Significant reductions in fPSA and hK2 were observed after only 16 and 8 hours, respectively. fPSA and hK2 showed similar elimination patterns, decreasing to 42% and 44% of their original levels compared to cystatin C, which was at 44% after 160 hours. The median half-lives of fPSA and hK2 were 17.4 and 11.5 hours, respectively. CONCLUSIONS: These results verify the hypothesis that fPSA and hK2 are eliminated from the blood circulation by glomerular filtration and severe renal failure influences the levels of the 2 proteins in serum.     

Elevation of serum transforming growth factor-β1 Level in patients with metastatic prostate cancer

We measured serum transforming growth factor β1 (TGF-b1) levels in patients with untreated prostate cancer and compared them with other prognostic indicators, specifically serum prostate-specific antigen (PSA) and the Gleason histopathologic grading score. Prior to treatment, the Sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure TGF-b1 concentrations directly in sera from 55 patients with prostate cancer (21 localized and 34 metastatic), 13 age-matched healthy male control subjects, and 8 patients with benign prostatic hyperplasia (BPH). Serum TGF-b1 levels in patients with lymph node and/or distant metastases were significantly higher than in patients with localized disease (p = 0.0003), but did not differ significantly among localized cancers as to tumor extension. Ten of 11 prostate cancer patients whose serum TGF-b1 was higher than an arbitrary cut-off value of 60 ng/ml had lymph node or distant metastasis (specificity 95.20, although in 24 of 34 metastatic patients serum TGF-b1 levels were less (sensitivity 29.4%). The correlation between serum TGF-b1 and tumor grade as assessed by the Gleason scoring system was weak (r = 0.340). Moreover, serum TGF-b1 was not correlated with the serum PSA level. Interestingly, there was an inverse correlation between serum TGF-b1 in the prostate cancer patients and patient age at diagnosis (r = -0.406). These findings suggest that elevation of the serum TGF-b1 levels reflects certain malignant potentials associated with metastasis that are unpredictable by PSA and the Gleason scoring system.     

Age-specific reference levels of serum prostate-specific antigen and prostate volume in healthy Arab men

OBJECTIVE; To determine age-specific reference ranges for serum prostate-specific antigen (PSA) concentration and prostate volumes in a population of healthy Arab men. SUBJECTS AND METHODS: Blood samples were taken from 396 healthy Arab men (from Kuwait and Oman) aged 15-79 years and from across the social spectrum. Men aged >40 years had a digital rectal examination and transrectal ultrasonography of the prostate to determine prostate volume. The serum PSA level was measured using commercial kits, and age-specific ranges for PSA levels and prostate volume determined. RESULTS: The serum PSA ranges (ng/mL) for each age range in Arab men were: 40-49 years, 0-0.9; 60-69, 0-2.7; 70-79, 0-5.5 ng/mL; the respective prostate volumes were 8-22, 9-30 and 10-33 mL. The serum PSA level and prostate volume correlated with age (P < 0.001). Arab men had lower serum PSA levels and prostate volumes than those reported for Caucasians, but similar to those reported for Asians (Japanese and Chinese). CONCLUSION: These results indicate that Arab men have lower PSA levels and prostate volumes than Caucasians. The levels are slightly lower than those reported in the Japanese and, as in the Japanese, low PSA levels and small prostate volumes might be related to the low incidence of clinical prostate cancer in Arab men.     

Serum osteoprotegerin (OPG) levels are associated with disease progression and response to androgen ablation in patients with prostate cancer

BACKGROUND: Osteoprotegerin (OPG) is a tumour and/or bone derived factor that may protect tumour cells from apoptosis. In this study, we have measured serum OPG levels in untreated prostate cancer patients with advanced prostate cancer compared to patients with organ confined disease and in treated patients receiving androgen ablation. METHODS: Serum OPG levels were measured by ELISA in samples collected from 104 patients with either newly diagnosed (n = 59) or advanced prostate cancer treated by androgen ablation (n = 45) and compared with levels in serum from patients with benign prostatic hyperplasia (BPH) (n = 10) and young healthy men (n = 10). RESULTS: Untreated patients with locally advanced disease had significantly higher OPG levels than those with organ confined disease. Patients with advanced disease responding to androgen ablation (serum PSA < 1 ng/ml) had serum OPG levels that were significantly lower than those with clinically progressing disease (PSA > 10 ng/ml). OPG levels in the latter were not significantly different from levels in patients with early signs of biochemical progression (PSA >1 but <10 ng/ml). CONCLUSIONS: OPG is a potential new marker, which is elevated in the serum of patients with advanced prostate cancer and may be an indicator of early disease progression.     

Mass screening for prostate cancer in patients with end-stage renal disease: a comparative study

OBJECTIVE: To determine the usefulness of prostate-specific antigen (PSA) screening for prostate cancer in patients with end-stage renal disease (ESRD), as although serum PSA is effective in the early detection of this cancer in the general population, there are few reports of its utility in patients with ESRD. PATIENTS AND METHODS: Blood samples were obtained for PSA screening from April 2002 to September 2003; 1250 men with ESRD aged >50 years were compared with 1007 healthy control men aged >55 years, all in Kumamoto Prefecture, Japan. All men with a serum PSA level of >4.0 ng/mL were categorized as PSA-positive and were further assessed, including a prostate biopsy. RESULTS: There was a statistically significantly greater increase in PSA level with age in the ESRD group than in the healthy controls. The rate of cancer detection among men with a PSA level of >10 ng/mL was significantly higher in patients with ESRD than in healthy controls. Thirteen patients with ESRD and five healthy control men were finally diagnosed with prostate cancer. CONCLUSION: The serum PSA level was slightly higher and the incidence of prostate cancer at higher PSA levels appeared to be greater in men with ESRD than in healthy controls. The findings of this large study suggest that PSA screening is useful for the diagnosis of prostate cancer in these patients.     

The assessment of PTEN tumor suppressor gene in combination with Gleason scoring and serum PSA to evaluate progression of prostate carcinoma

OBJECTIVE: The purpose of the study was to determine if the tumor suppressor gene phosphate and tensin homolog (PTEN) (mutated in multiple advanced cancers 1) in combination with Gleason scoring and serum prostate specific antigen (PSA) could be employed to better predict the progression of prostate carcinoma. MATERIALS AND METHODS: The study group consisted of 43 patients with benign prostate hyperplasia (BPH), 15 with organ confined prostate carcinoma (OCPCa), and 18 with advanced prostate carcinoma (APCa). Prostate tissue samples were obtained from radical prostatectomy, transurethral resection, and TRUS guided trans-rectal needle biopsy and then evaluated for biomarker expression. The clinical stage was assessed according to tumor node metastasis classification and grade according to Gleason system. Serum PSA was measured by conventional techniques and Western blotting analysis was used to determine PTEN expression in the primary tissue. Multivariate analysis was performed to analyze whether these markers could individually predict the progression of prostate carcinoma. RESULTS: APCa patients displayed higher Gleason scores and serum PSA levels. But much lower PTEN expression was detected in prostate of APCa patients compared to patients with BPH or OCPCa. Hormone refractory (HR) and hormone sensitive (HS) APCa cases did not yield any significant differences in terms of Gleason scoring, serum PSA and PTEN expression. PSA levels were significantly higher in patients with OCPCa or APCa compared to patients with BPH. CONCLUSION: Our results suggested that both PTEN and serum PSA appeared to be useful as independent markers to depict the nature of tumor behavior as benign or malign. In addition, PTEN also appeared to be useful as an independent marker to predict the progression of prostate carcinoma.     

The value of γ-seminoprotein in combination with prostate specific antigen in detecting prostate cancer

BACKGROUND: The present study was undertaken to investigate the value of gamma-seminoprotein (gamma-Sm) and the gamma-Sm/prostate specific antigen (PSA) ratio in combination with serum PSA in detecting prostate cancer. METHODS: Prostate specific antigen, gamma-Sm and the gamma-Sm/PSA ratio were evaluated in 112 patients with untreated prostate cancer and 90 patients without prostate cancer who had serum PSA and gamma-Sm levels above their respective detection limits. RESULTS: When data for all of the patients were analyzed, serum PSA and gamma-Sm levels were significantly higher and the gamma-Sm/PSA ratio was significantly lower in patients with prostate cancer than patients without prostate cancer. The serum PSA and gamma-Sm levels significantly increased and the gamma-Sm/PSA ratio significantly decreased with advancing clinical stage in patients with prostate cancer. Among the patients with serum PSA levels ranging from 1.8 to 6 ng/mL, the gamma-Sm/PSA ratio was significantly lower (P < 0.05) and gamma-Sm levels were lower (P = 0.054) in the patients with prostate cancer than in those without prostate cancer, but serum PSA levels were not significantly different (P = 0.53). A receiver operating characteristic (ROC) analysis demonstrated that the areas under the ROC curves were 0.54 for PSA, 0.65 for gamma-Sm and 0.69 for the gamma-Sm/PSA ratio for prediction of prostate cancer in the PSA range from 1.8 to 6 ng/mL, although the ROC analysis suggested that the gamma-Sm/PSA ratio does not provide significant advantage over PSA in detecting prostate cancer when all of the patients were analyzed. CONCLUSIONS: These results suggest that the gamma-Sm/PSA ratio and gamma-Sm may facilitate differentiation between patients with and without prostate cancer who have intermediate PSA levels.     

Clinical usefulness of serum antip53 antibodies for prostate cancer detection: a comparative study with prostate specific antigen parameters

PURPOSE: Alterations in the p53 tumor suppressor gene located on human chromosome 17p13.1 are currently the most common genetic abnormalities associated with many different types of human malignancies. Recently serum p53 antibodies (p53-Abs) have been detected in the serum of patients with various cancers. To evaluate the clinical usefulness of serum p53-Abs we compared p53-Abs with prostate specific antigen (PSA) parameters in patients with benign prostatic disease (BPD) and prostate cancer. MATERIALS AND METHODS: Serum samples were obtained from 50 patients with BPD and 103 with histologically diagnosed prostate cancer, including T1c/2N0M0 in 50, T3N0M0 in 29 and TxNxM1 in 24. The serum p53-Abs titer was assessed by enzyme-linked immunoabsorbent assay using a MESCUP Kit II (Medical and Biological Laboratories Co., Ltd., Nagoya, Japan) antip53 test. Free and total PSA was measured using an Architect (Dinabott, Chicago, Illinois) PSA kit. The clinical values of p53-Abs were compared with total PSA, PSA density (PSAD), PSA density of the transition zone (PSATZD) and the free-to-total PSA ratio using ROC curves. RESULTS: All patients with prostate cancer had significantly higher total PSA, PSAD, PSATZD and p53-Abs than patients with BPD. While total PSA, PSAD, PSATZD and free-to-total PSA ratios were associated with stage progression, serum p53-Abs were not related to clinical stage. The Gleason sum 5 or less group had a higher level of p53-Abs than higher Gleason sum groups. Patients with T1c cancer had significantly higher p53-Abs than those with BPD. According to ROC curve analysis to distinguish prostate cancer from BPD the p53-Abs titer had the greatest AUC in the overall patient population and in patients without digital rectal examination findings. CONCLUSIONS: These results suggest that p53-Abs might be helpful in the clinical decision to perform prostate biopsy. In the current study the serum p53-Abs titer had the most useful validity in discriminating between prostate cancer and BPD in the overall patient population and in patients with normal digital rectal examination.     

Western blot assay for prostate-specific membrane antigen in serum of prostate cancer patients

There is a need for the development of new diagnostic tools for the early detection of prostate cancer. A candidate molecule for a new screening test is a prostate-specific membrane antigen (PSM) recognized by the monoclonal antibody 7E11.C5. We carried out studies aimed at identifying PSM in the serum of normal and benign prostatic hyperplasia (BPH) donors and patients with adenocarcinoma of the prostate, in order to judge whether the development of a serum assay using this marker was feasible. By Western blotting, we found significant levels of PSM in serum samples from prostatic cancer patients, in the seminal fluid of pooled normal donors, in BPH patients, and in normal male sera. Similar to prostate-specific antigen (PSA), PSM was present in seminal plasma in higher concentrations than in serum, and PSM levels in prostatic cancer patients were significantly higher than in normal controls. These data suggest that the development of an assay utilizing the PSM and new monoclonal antibodies directed against the antigen, could provide a feasible test for prostatic cancers. © 1994 Wiley-Liss, Inc.     

Serum keratinocyte growth factor measurement in patients with prostate cancer

PURPOSE: Keratinocyte growth factor (KGF) is a stromally derived growth factor important in mediating androgen induced activities in benign prostatic hyperplasia (BPH) and prostate cancer. We assessed whether serum KGF could be used as a molecular marker in patients with prostate cancer. MATERIALS AND METHODS: Using a modified double sandwich enzyme-linked immunosorbent assay, we measured serum KGF in 56 men with prostate cancer and 81 men with BPH. Comparative analyses were made with total serum prostate specific antigen (PSA), disease stage and clinical grade. RESULTS: Following optimization, a sensitive and reproducible assay for serum KGF measurement was developed. Serum KGF levels tend to be higher in men with BPH compared to those with prostate cancer (1,242 and 828 pg./ml., respectively). A weak but significant linear relationship between PSA and KGF (p = 0.034) was found in patients with BPH. There was no association between KGF and tumor grade or stage but there was a strong positive linear relationship between PSA and KGF (p = 0.006, R(2) = 68.3%) in low grade tumors. In those men with serum PSA less than 10 ng./ml. KGF levels were significantly higher in BPH compared to prostate cancer cases (965 +/- 245 and 133 +/- 61.3 pg./ml., respectively, p = 0.0058). Using a KGF threshold range of 500 to 900 pg./ml., specificity for detecting BPH was 88% to 100% and the positive predictive value was 92% to 100%. CONCLUSIONS: We have optimized a reproducible and sensitive enzyme-linked immunosorbent assay system for the measurement of serum KGF. Overall KGF levels tend to be lower in patients with prostate cancer than with BPH. In patients with serum PSA less than 10 ng./ml. serum KGF levels were significantly higher in the BPH compared to the prostate cancer group. A large prospective study is indicated to assess the role of serum KGF measurement in patients with prostate cancer.     

Prostate-specific antigen assay using whole blood samples spotted on filter paper and its application to mass screening for prostate cancer

AIM: The disc assay system for prostate-specific antigen (PSA) is a novel technique using a small amount of whole blood on filter paper. The accuracy of this assay system and its feasibility for use in prostate cancer mass screening were evaluated. METHODS: In the first arm of the study, to evaluate the accuracy of the disc assay system, PSA values were determined by both a disc assay system and a standard serum assay system using the same blood samples obtained from 420 outpatients. In the second arm of the study, the feasibility and reliability of the disc assay system were examined in prostate cancer mass screening. A total of 2475 men were screened by the disc assay (disc group) and 3348 men were screened by the standard serum assay (serum group) in the first step of mass screening. In the second step of the screening in the disc group, 101 men underwent PSA tests by a standard serum assay, then the first PSA values determined by the disc assay were compared with the second PSA values determined by the standard serum assay. In the second step of the screening in the serum group, 94 men underwent additional PSA tests by a serum assay, and then the first PSA values were compared with the second PSA values. Two men in each group were excluded from analysis because the true PSA values of the first step were not available (more than 50 ng/mL). RESULTS: The PSA values determined by the disc assay closely correlated with those obtained by the standard assay (r = 0.987) in 295 outpatients with PSA levels between 1.0 and 20 ng/mL. In the PSA mass screening, the PSA values determined in the first step closely correlated with those in the second step both in the disc group (r = 0.916) and in the serum group (r = 0.845). A significant dissociation of the two PSA values was observed in seven of 99 men in the disc group and in three of 92 men in the serum group. However, there was no statistical significance in the incidence of dissociation in the two PSA values between the disc group and the serum group. CONCLUSIONS: The disc assay system seems to be a sensitive and accurate assay system. The feasibility and reliability of the disc assay system were well demonstrated in the field during prostate cancer mass screening.