Prostatic Acid Phosphatase Levels Research Articles

Isolation and partial characterization of an epithelial cell line (RPE-F344) from the regenerating prostate of a normal adult male rat.

Normal prostate epithelial cells are difficult to propagate in vitro without experimental immortalization. The goal of this study was to isolate and characterize a propagable epithelial cell line from normal adult rat prostate. Enrichment of proliferation-competent cells was accomplished in vivo by initiating a single cycle of prostatic involution/regeneration. The RPE-F344 cell line was established from an androgen-deprived, involuted prostate four days after the initiation of regeneration by administration of testosterone. The cell line has been cultured in vitro for >50 passages, forms a uniform monolayer in culture, exhibits contact inhibition at confluence, and does not form colonies in soft agar. Immunocytochemical and RT-PCR analyses demonstrated that the RPE-F344 cells express anti-apoptotic genes associated with cell survival, and several growth factor receptors important in prostate development and homeostasis. RPE-F344 cells are p27kip1 negative, telomerase positive, and express high molecular weight cytokeratins specific for prostatic basal cells. They also express low levels of androgen receptor (AR) and prostatic acid phosphatase (PAP); features associated with secretory luminal epithelial cells. RPE-F344 cells are maintained in vitro without androgen supplementation, but addition of 15nM dihydrotesterone (DHT) to the culture media results in a significant but transient enhancement of cellular proliferation. Establishment of RPE-F344-like colonies from rat prostate is limited to the ventral and dorsal lobes of the prostate 2-4 days after initiation of regeneration, suggesting that RPE-F344 cells may originate from a stem cell-like compartment that is responsible for regenerative repopulation.

The age of the urologist affects the postoperative care of prostate carcinoma patients

Strategies utilized by urologists in managing prostate carcinoma patients after radical prostatectomy vary appreciably. The reason for this is unclear. The authors investigated the effect of practitioner age on management strategies. From among the total of 12,500 American Urological Association (AUA) members, 4467 were randomly selected to receive a custom-designed survey about their care of prostate carcinoma patients after radical prostatectomy. Respondents were asked to describe their follow-up practices for patients treated with curative intent, their motivations regarding postoperative surveillance, their methods of evaluating a postoperative increase in serum prostate specific antigen (PSA) level, and their choices of treatment for patients with recurrent prostate carcinoma. One thousand fifty responses were analyzed. There was a statistically significant influence of practitioner age on the management of at-risk patients, but it was quite small. The typical workup for an elevated postoperative serum PSA level also varied significantly according to practitioner age; older urologists ordered more serum prostatic acid phosphatase levels and computed tomography scans of the abdomen and pelvis, whereas younger urologists ordered more bone scans. The treatment of recurrent prostate carcinoma did not vary significantly according to urologist age. The opinions of older urologists regarding the survival benefits of postoperative surveillance were considerably different from the opinions of their younger colleagues. The results of this study suggest that urologist age accounts for some of the variation in the postoperative management of prostate carcinoma patients. Differences in beliefs regarding the benefits of surveillance may be partially responsible for this. Persuasive clinical research will probably be required to increase the uniformity of practice in this important area.

Structural Origins of l(+)-Tartrate Inhibition of Human Prostatic Acid Phosphatase

Acid phosphatase activity in the blood serum is usually separated into tartrate-resistant and tartrate-refractory, which is reported as the prostatic acid phosphatase level. Human prostatic acid phosphatase crystals soaked in N-propyl-L-tartramate were used to collect x-ray diffraction data to 2.9 A resolution under cryogenic conditions. Positive difference electron density, corresponding to the inhibitor, was found. The quality of the electron density maps clearly shows the orientation of the carboxylate and N-propyl-substituted amide groups. The hydroxyl group attached to C3 forms two crucial hydrogen bonds with Arg-79 and His-257. Previous crystallographic studies compiled on the tartrate-rat prostatic acid phosphatase binary complex (Lindqvist, Y., Schneider, G., and Vihko, P. (1993) J. Biol. Chem. 268, 20744-20746) erroneously positioned D-tartrate into the active site. Modeling studies have shown that the C3 hydroxyl group on the D(-)-stereoisomer of tartrate, which does not significantly inhibit prostatic acid phosphatase, does not form strong hydrogen bonds with Arg-79 or His-257. The structure of human prostatic acid phosphatase, noncovalently bound in N-propyl-L-tartramate, is used to develop inhibitors with higher specificity and potency than L(+)-tartrate.

Prognosis of Patients with Prostate Carcinoma Presenting as Nonregional Lymph Node Metastases

Objective: The mode of progression in patients with prostate cancer with metastasis to nonregional lymph nodes was examined in order to know whether the site of metastasis effects the prognosis of prostate cancer. Methods: From 1986 to 1995 at the Chiba University Hospital, 205 cases of prostatic cancer with distant metastases were experienced. In 17 of them, nonregional lymph node metastases were observed at the diagnosis, of whom 10 also had bone metastases. Results: There was no statistical difference in prognosis between 17 patients with nonregional lymph node metastases and remaining 188 patients with metastatic prostate cancer. In all patients metastasized to nonregional lymph nodes, serum prostate-specific antigen and/or prostatic acid phosphatase levels were elevated. Anti-androgen therapy was effective in 15 cases and 5-year survival rate was 45.8%. Patients without bone metastases at the initial diagnosis could survive longer than those with metastases to bone (p < 0.05). Conclusions: From these observations, endocrine therapy was effective even in patients with distant lymph node metastases.

Prostate cancer in African-American men: outcome following radiation therapy with or without adjuvant androgen ablation

Purpose: To compare the outcome of irradiated clinically localized prostate cancer in African-American and white patients. Methods and Materials: This was a retrospective review of 1,201 men, 116 African-American and 1,085 white, with T1–T3, N0/NX, M0 prostate cancer receiving external radiation between 1987 and 1996. Pretreatment characteristics, treatment parameters, and outcome (relapse or rising prostate-specific antigen [PSA] levels, local recurrence, metastatic relapse, and survival) were compared between the groups using univariate and multivariate statistical methods. Results: There were no significant differences between African-American and white patients in T-stage, Gleason score, prostatic acid phosphatase (PAP) level, and testosterone level. African-Americans had a significantly lower incidence of abnormal digital rectal findings and a proportionally higher incidence of obstructive urinary symptoms at presentation and tended to be somewhat younger. A major difference between the two groups was in the significantly higher PSA levels among African-Americans (median, 14 ng/ml) than among white patients (median, 9.5 ng/ml). This translated into a higher incidence of unfavorable disease according to our criteria (39% vs. 25%) among African-Americans and, thus, to the more frequent use of adjuvant androgen ablation and to somewhat higher radiation doses in these patients. With a median follow-up of 42 months the overall 6-year freedom from relapse for African-Americans was 63% compared to 61% for whites ( p = 0.634). We found no significant differences in biochemical relapse rates between any subgroups of African-Americans and whites. Specifically, even patients who did not have androgen ablation, when stratified by PSA levels, had similar outcomes regardless of race. Likewise, local recurrence and metastasis rates were not significantly different between the two groups. Conclusions: Although African-American patients tend to have higher pretreatment PSA levels than white patients, the outcome for the disease is similar in the two groups when stratified by known pretreatment prognostic factors. Our data provide no evidence for the hypothesis that prostate cancer in African-Americans is intrinsically more virulent than in whites.

Renal tubular reabsorption of phosphate is positively related to the extent of bone metastatic load in patients with prostate cancer.

Osteolytic metastases are often associated with decreased renal tubular reabsorption of phosphate. There is, however, no specific data on phosphate metabolism in metastases from prostatic cancer, which are generally osteoblastic. The aim of the present study was to investigate renal handling of inorganic phosphate (Pi) in prostatic cancer, in patients without or with skeletal metastases of various extents. Forty-eight patients were the subjects of this study. There were 39 with malignant disease, of whom 27 had bony metastases. Nine other patients had benign prostate hyperplasia. Biochemical indexes of prostatic tumor, renal tubular reabsorption of calcium and Pi, biochemical markers of bone remodeling, and relevant calciotropic hormones were measured and analyzed in relation to the extent of skeletal metastases, as assessed by bone scintigraphy. A higher bone metastatic load was associated with significantly greater prostate-specific antigen and prostatic acid phosphatase levels (P < 0.05), increased levels of biochemical markers of bone formation (P < 0.05) and resorption (P < 0.001), higher maximal renal tubular reabsorption of Pi (TmPi/GFR; P < 0.05), and higher urinary cAMP excretion (P < 0.05). Nine patients among those with bone metastases (n = 27) had higher TmPi/GFR than metastasis-free patients. These had a greater value of osteocalcin (P < 0.001). Also, 8 of these had relatively more extensive skeletal metastatic load. In patients with prostatic cancer, high skeletal metastatic load was accompanied by increased TmPi/GFR despite higher urinary cAMP excretion, which is supposed to reduce the TmPi/GFR. These results support the hypothesis that renal tubular reabsorption of Pi is capable of adaptation to meet demands for minerals in the face of enhanced bone formation.

Prostatic hyperplasia: an unknown feature of acromegaly.

This study was designed to investigate whether GH and insulin-like growth factor I (IGF-I) excess could lead to the development of benign prostatic hyperplasia and/or prostatic carcinoma. Prostatic diameters and volume as well as the occurrence of prostatic diseases were studied by ultrasonography in 10 untreated acromegalic patients less than 40 yr of age and 10 age- and body mass index-matched healthy males. Serum GH, IGF-I, PRL, testosterone, dihydrotestosterone, prostate-specific antigen, and prostatic acid phosphatase levels were assessed. All patients had secondary hypogonadism, as diagnosed by low testosterone levels, and 4 of 10 patients had hyperprolactinemia. After 1 yr of treatment with octreotide (0.3-0.6 mg/day), ultrasound scan and hormone parameters were repeated. The 4 hyperprolactinemic acromegalics were treated with octreotide and cabergoline (1-2 mg/week) to suppress PRL levels. Symptoms due to prostatic, seminal vesicle, and/or urethral disorders or obstruction were experienced by neither acromegalics nor controls. Digital rectal examination revealed no occurrence of prostatic nodules or other abnormalities. Compared to healthy subjects, a remarkable increase in transversal prostatic diameter and volume was observed in acromegalics. In healthy subjects, prostate volume ranged from 15.1-21.8 mL, whereas in acromegalics it ranged from 21.8-41.8 mL. Similarly, an increased median lobe was observed. In fact, the transitional zone diameter was just detectable in 5 of 10 controls, whereas it was measurable in all acromegalics (18 +/- 1.2 vs. 2.8 +/- 0.3 mm; P < 0.001). The prevalence of periurethral calcifications was more than doubled in acromegalics (50%) compared to that in controls (20%). Treatment with octreotide for 1 yr produced normalization of circulating GH and IGF-I levels in 7 of 10 patients. In these 7 patients, ultrasound evaluation showed a significant reduction of the antero-posterior diameter (26.1 +/- 1 vs. 28.9 +/- 1.6 mm; P < 0.01), the transversal diameter (44.9 +/- 2 vs. 48 +/- 2 mm; P < 0.01), and the cranio-caudal diameter (36.5 +/- 1 vs. 41.3 +/- 1.5 mm; P < 0.001), whereas the transitional zone diameter was unchanged (16.4 +/- 1.5 vs. 17.4 +/- 1.7 mm). As a consequence, a significant decrease in prostate volume was recorded (22.1 +/- 1.1 vs. 29.8 +/- 2.5 mL; P < 0.001). Prostate volume increased in 2 of the 3 patients who did not achieve normalization of GH and IGF-I after octreotide treatment. Finally, after treatment, serum testosterone levels were significantly increased (from 1.5 +/- 0.3 to 3.5 +/- 0.3 microg/L), whereas dihydrotestosterone, dehydroepiandrosterone sulfate, delta4-androstenedione, 17beta-estradiol, prostate-specific antigen, and prostatic acid phosphatase were unchanged. Serum PRL levels were suppressed after cabergoline treatment in all 4 hyperprolactinemic patients throughout the study period. In conclusion, prostate enlargement occurs in young acromegalics with a higher than expected prevalence of micro- and macrocalcifications. This suggests that a careful prostate screening should be included in the work-up and follow-up of acromegalic males.

Expression of E-cadherin in primary prostate cancer: correlation with clinical features.

To correlate the immunohistochemically detected loss of E-cadherin expression with patient age, clinical and biological variables, and to investigate the prognostic value of these variables for the relapse-free and overall survival of patients with different stages of newly diagnosed prostate cancer. Sixty-seven patients (median age 63 years, range 48-78) undergoing radical prostatectomy for the treatment of primary prostate cancer were assessed to determine whether age, tumour stage, histological grading, serum levels of prostate specific antigen and prostatic acid phosphatase, regional lymph node status and E-cadherin expression were prognostic factors for relapse-free and overall survival. With a median (range) follow-up of 54 (3-193) months, there was no independent prognostic value of decreased E-cadherin expression for the long-term or recurrence-free survival of patients, using a threshold value of 40% for the relative amount of positively stained tumour cells, or for any other threshold value calculated (25%, 60% or 75%). However, comparing a follow-up of 16 months in patients with < 40% positivity and 46 months in patients with > or = 34% positivity, those patients retaining E-cadherin expression had a significantly longer recurrence-free interval after radical prostatectomy (P < 0.01). The value of E-cadherin expression as an additional independent prognostic variable for patients with primary prostate cancer is questionable.

CasodexTM 10–200 mg Daily, Used as Monotherapy for the Treatment of Patients with Advanced Prostate Cancer

Objectives: To evaluate the efficacy, tolerability, endocrinological effects and the pharmacokinetics of Casodex^TM, when given as monotherapy during daily dosing of 10–200 mg to patients with advanced prostate cancer. Methods: A total of 390 patients with advanced prostate cancer were treated for a minimum of 12 weeks with a daily monotherapy dose of Casodex. The doses ranged from 10 to 200 mg. Objective assessments of efficacy included: review of measurable metastases, prostate dimension, prostatic acid phosphatase and prostate-specific antigen (PSA) levels. Subjective assessments of efficacy included review of urological symptoms, performance status, bone scan and analgesic requirement. Pharmacokinetic samples were taken at various time points up to 3 months, and assayed using an achiral HPLC method. Results: Clear objective responses were observed, particularly at doses of 50 mg and above. Specifically, the median percentage decrease in PSA at 50 mg was 90.0%, and at 100 and 200 mg it was 93.4 and 94.8%, respectively. Up to 53% of symptomatic patients demonstrated a subjective response at 3 months. Casodex was well tolerated at all doses with no effect on haematological or cardiovascular parameters and no effect on renal function. The expected pharmacological effects of potent antiandrogen therapy, such as breast tenderness (58%), gynaecomastia (48%), and hot flushes (17%), were reported, but these incidences reflected the direct eliciting of these events. The intrinsic efficacy of Casodex was demonstrated despite increases of 60% in testosterone levels. However, this increase reached a plateau after 4–12 weeks of therapy, but the majority of values remained within the normal range. Casodex has a half-life of approximately 1 week, enabling once-daily dosing with no effect of age or renal impairment on its pharmacokinetics. Conclusion: Casodex has a favourable side effect profile compared with the known safety profiles of other antiandrogens and has demonstrated intrinsic efficacy. Casodex warrants further investigation as a monotherapy for the management of advanced prostate cancer.

Bayer immuno 1™ PSA assay: An automated, ultrasensitive method to quantitate total PSA in serum

The Bayer Immuno 1 PSA Assay measures total PSA in human serum and demonstrates excellent performance with an interassay CV < or = 3.4% and a biological detection limit of 0.03 microgram/L. No significant interference from common hormonal and chemotherapeutic drugs, kallikrein, prostatic acid phosphatase, and trypsin, or elevated levels of total bilirubin, hemoglobin, triglycerides, and IgG was observed. The 95th percentile values for healthy individuals increased with age from 3.0 micrograms/L for males 50-59 years and 3.3 micrograms/L for males 60-69 years, to 4.6 micrograms/L for males > or = 70 years. Clinical studies with retrospective samples demonstrated correspondence between serial measurements of PSA and clinical outcome for 98% of 159 prostate cancer patients. Clinical sensitivity for patients with clinical evidence of disease, untreated at the time of specimen draw, increased with increasing stage from 77.5-100%. Specificity of 60-70% for BPH and other benign urogenital diseases was consistent with previous findings. Bayer Immuno 1 PSA Assay values for 2131 specimens from healthy subjects and patients with prostate cancer, BPH, and other malignant and nonmalignant diseases correlated well with the Abbott IMx PSA Assay over the range 0.0-6,238 micrograms/L (Y = 1.10 x + 0.02). The Bayer Immuno 1 PSA Assay provides automated ultrasensitive, precise, and equimolar measurement of total PSA in human serum.

The effect of dihydrotestosterone on transcription of prostatic acid phosphatase mRNA in human hyperplastic gland.

The effect of 5alpha-dihydrotestosterone (DHT) on the level of human prostatic acid phosphatase (hPAP) mRNA was studied using tissue slices from various benign prostatic hyperplastic glands. The absence of DHT in the incubation medium led to a gradual, significant decrease of the hPAP mRNA level. Addition of the hormone induced hPAP mRNA in a time- and dose-dependent manner. The maximal 2-4-fold induction by 10(-9) M DHT was observed after 3-5 h of incubation, and then the hPAP mRNA level was 6-20-fold higher than that in a parallel sample incubated without DHT. The results suggest that DHT is necessary to sustain the expression of hPAP in hyperplastic prostates.

Low serum testosterone and a younger age predict for a poor outcome in metastatic prostate cancer.

Carcinoma of the prostate gland is one of the most common malignancies in males. This study was undertaken to determine which factors predict the course and outcome of patients treated with first line hormonal manipulation. A total of 144 patients with Stage D2 prostate cancer who received androgen deprivation therapy were studied. Pretreatment parameters analyzed were age, performance status, analgesia usage, concurrent disease, histologic differentiation, hemoglobin, leukocyte and platelet count, serum creatinine, alkaline phosphatase, lactate dehydrogenase, prostate specific antigen, total and prostatic acid phosphatase, serum testosterone, follicle stimulating and luteinizing hormone levels, number of metastatic sites and bone scan grade. Only initial serum testosterone (> 10 nmol/l) had a positive impact on response (p = 0.0304), whereas age older than 60 years had a positive impact on time to progression (16 vs. 11 months, p = 0.0414). Both serum testosterone (26 vs. 20 months, p = 0.003), and age (28 vs. 17 months, p = 0.036) had a significant influence on overall survival. Low testosterone, indicating androgen independence, and a younger age, seem to result in a more aggressive disease and a poorer prognosis in advanced prostate cancer.

Prostatic acid phosphatase levels (enzymatic method) from completely sectioned, clinically benign, whole prostates

Clinically benign, whole untrimmed prostates were obtained from 104 patients at autopsy, completely sectioned, and examined microscopically. The histological and gross findings of the prostate were correlated with premortem prostatic acid phosphatase levels (PAP, enzymatic method, ACA, Dupont Co.) to determine how often carcinoma of the prostate (CAP) affected PAP levels and to identify other findings within the prostate associated with elevated PAP levels. Sixty (58%) prostates did not have CAP, 34 (33%) had CAP smaller than 1 ml in volume, and 10 (10%) had CAP larger than 1 ml in volume. PAP levels were elevated (greater than 1 U/L) in 8 of 60 (13%) prostates without CAP, in 2 of the 34 (6%) prostates with CAP smaller than 1 ml, and in 1 of the 10 (10%) prostates with CAP larger than 1 ml. These differences were not statistically significant. Likewise, a statistically significant correlation between PAP levels and patient age, patient race, severe inflammation, of high grade prostatic intraepithelial neoplasia (PIN) was not found. However, there was a statistically significant correlation between PAP levels and prostate weight (p < 0.0001). This study suggest that PAP cannot distinguish between patients with clinically undetected CAP and patients without CAP. Furthermore, elevated PAP levels are often not due to metastatic CAP and additional evidence should be present, even in patients with known CAP, before an elevated PAP level is considered to be conclusive evidence of metastatic CAP.

Prostatic acid phosphatase levels (enzymatic method) from completely sectioned, clinically benign, whole prostates

Prostatic acid phosphatase levels (enzymatic method) from completely sectioned, clinically benign, whole prostates

Effects of androgen therapy on prostatic markers in hemodialyzed patients.

We have prospectively studied the evolution of serum levels of the prostatic-specific antigen and prostatic acid phosphatase in 14 male hemodialyzed patients, receiving a cycle of nandrolone decanoate (200 mg intramuscularly, once a week, for six months) as treatment for anemia. Androgen administration did not produce significant increases in serum concentrations of both tumor markers (basal: 0.9 +/- 0.5 and 0.7 +/- 0.3 ng/ml; at six months: 1.3 +/- 1.1 and 0.8 +/- 0.7 ng/ml respectively). Only one patient had a value of prostatic-specific antigen over the normal range: 4.2 ng/mol at the sixth month period, with a rapid decrease after the withdrawal of androgens. All the remaining values of both markers were within the normal range. In another six patients undergoing a prolonged treatment with androgens (between 9 to 24 months), the serum levels of prostatic-specific antigen and prostatic acid phosphatase were within the normal range in all of them. Nandrolone decanoate administration does not induce increases in prostate tumor markers when it is used as treatment for anemia in hemodialyzed patients.

Plasma Neuroendocrine Markers in Patients with Benign Prostatic Hyperplasia and Prostatic Carcinoma

Purpose Approximately 50 percent of all malignant prostatic tumors contain neuroendocrine cells, which cannot be attributed to small cell prostatic carcinoma or carcinoid-like tumors, and which represent only 1 to 2 percent of all prostatic malignancies. Only limited data are available concerning the plasma levels of neuroendocrine markers in patients with prostatic tumors. Therefore, we determined the incidence of high plasma levels of neuroendocrine markers in patients with benign and malignant prostatic disease. Materials and Methods The presence of elevated plasma neuropeptide levels was investigated in 135 patients with prostatic carcinoma and 28 with benign prostatic hyperplasia. Plasma chromogranin A, neurone-specific enolase, substance P, calcitonin, somatostatin, neurotensin and bombesin levels were analyzed by immunoassays, and were compared to clinical and pathological stages of disease. Plasma prostatic acid phosphatase and prostate specific antigen levels were also determined. All patients were followed for at least 2 years after inclusion in the study. Results Significantly elevated levels of chromogranin A were detected in 15 percent of patients with prostatic carcinoma before any treatment. During hormone resistant prostate cancer progression plasma chromogranin A and neuron-specific enolase levels were elevated in 55 percent and 30 percent of the patients, respectively. In patients with stage D3 disease survival curves were generated by the Kaplan-Meier method, and log rank analysis revealed a statistically significant difference between groups positive and negative for chromogranin A. Substance P and bombesin were also occasionally elevated in prostatic tumors. Determination of neuroendocrine differentiation by neuron-specific enolase or chromogranin A immunoassays was not helpful in the prediction of progressive localized prostatic carcinoma. Conclusions Future studies of plasma neuropeptide levels should confirm whether these parameters can be used as prognostic markers during late progression of prostatic carcinoma or for the selection of patients suitable for evaluation of new antineoplastic drugs known to be active against neuroendocrine tumors.

Estramustine-binding protein to dihydrotestosterone ratio in human prostatic carcinoma: a new marker for predicting disease progression.

To elucidate the clinical significance of estramustine-binding protein (EMBP) in human prostatic carcinoma (PC) as an indicator for predicting disease progression. EMBP concentrations in prostate tissue samples taken from 35 patients with benign prostatic hyperplasia (BPH), 33 patients with prostatic carcinoma (PC) taken before treatment, and from nine patients with hormone-refractory PC (hr-PC) were measured by radioimmunoassay using an antibody raised against rat EMBP. The dihydrotestosterone (DHT), prostatic acid phosphatase (PAP), prostate-specific antigen (PSA) and zinc levels in the tissue were also measured. The EMBP concentration in well differentiated PC (W-PC) samples was no higher than in samples of BPH tissue, whereas concentrations in moderately differentiated PC (M-PC) and poorly differentiated PC (P-PC) were significantly higher (P < 0.01 and P < 0.005, respectively); the highest levels were those in tissue from hr-PC (P < 0.001). Levels of PAP, PSA and zinc were significantly lower in tissue from PC than from BPH, while the differences in levels between W-PC, M-PC and P-PC were not significant. The EMBP to DHT ratio in the tissue increased significantly from W-PC through M-PC to P-PC and was greatest in hr-PC tissue. Conversely, the PAP:DHT, PSA:DHT and zinc:DHT ratios did not correlate with the progress of histological grade. In addition, the pre-treatment EMBP:DHT and zinc:DHT ratios in 14 patients who developed hr-PC within 3 years after the administration of estramustine phosphate were significantly higher when compared with the remaining 19 patients (P < 0.001 and P = 0.0184, respectively), whereas the PAP:DHT and PSA:DHT ratios showed no significant difference between the groups. Moreover, patients with a high EMBP:DHT ratio (> or = 82) had a low progression-free probability compared to those with a lower ratio. The androgen-dependent property of EMBP tends to decline with the transformation of prostatic tissue into biologically more malignant disease. The tissue EMBP:DHT ratio before treatment may be a good indicator of the individual malignant potential of PCs.

Prostatic acid phosphatase and prostate specific antigen in liver disease

Serum concentrations of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) were measured in 51 liver cirrhosis, 37 chronic active hepatitis (CAH) patients and 26 healthy individuals. Elevated PSA levels have been found in 2 of cirrhotic patients while no increase has been detected in CAH and controls. Serum PAP levels have been observed slightly increased in 2 patients with cirrhosis, 2 patients with CAH and 1 control case. Mean PSA and mean PAP values showed no significant difference between groups (p > 0.05). Serum PSA and PAP levels are reliable in diagnosing and monitoring prostate cancer in chronic liver patients and maintain their specificity in this situation.

Changes in serum levels of prostatic acid phosphatase and prostate specific antigen after luteinizing hormone-releasing hormone analogue administration in patients with metastatic prostatic cancer in relation to glandular differentiation.

Eighteen previously untreated patients with metastatic carcinoma of the prostate were treated with LHRH analogue. They were divided into 3 groups according to the degree of glandular differentiation. In all groups, a transient rise of PAP and PSA was observed after the LH and testosterone surge. However, relative values of LH, testosterone, PAP and PSA did not differ significantly among the 3 groups. These facts suggest that a transient rise of PAP and PSA is caused by testosterone surge independently from the degree of glandular differentiation after LHRH analogue administration in patients with advanced prostatic cancer.

The prognostic significance of tumor-associated markers p53, HER-2/neu, c-myc, v-H-ras, PCNA and EGFr of local and distant recurrence in localized human prostatic adenocarcinoma

The intracellular expression of the gene products of tumor-associated markers p53, proliferative cell nuclear antigen (PCNA), HER-2/neu, c-myc, H-ras, and epidermal growth factor receptor (EGFr) in 86 cases of localized prostatic adenocarcinoma was investigated immunohistochemically in formalin-fixed paraffin-embedded tissue sections after pretreatment with a novel antigen retrieval buffer. A scoring system was devised to assess strength, pattern, and combined strength/pattern of immunostainings in the nucleus and cytoplasm for each immunomarker. The results were evaluated to determine whether overexpression of the gene products in the nucleus and cytoplasm was predictive of local and/or distant tumor recurrence and whether their expression was associated with known clinical prognostic factors. There was no significant relation between p53, PCNA, HER-2/neu, c-myc, and H-ras protein expression with risk of recurrence. EGFr expression showed a trend of increasing risk of tumor recurrence with higher composite score. Analysis of the association with other known prognostic factors in prostatic adenocarcinoma showed that PCNA was significantly correlated with tumor stage while H-ras and HER-2/neu were marginally correlated with prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) pretreatment serum levels, respectively. Together our findings suggest that overexpression of these intracellular oncoproteins in the tumor cells may not play an important role in determining whether prostatic tumors are likely to recur in localized prostatic adenocarcinoma.