Prostate specific antigen and prostatic acid phosphatase measurements for the follow-up of patients with prostate cancer.

The clinical application of 84 prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) measurements for the follow-up of 36 patients with treated prostate cancer was retrospectively examined by case study. Clinicians use several risk markers including serum levels of PSA and PAP to monitor prostate cancer progression or stability. These results of PAP and PSA tests were either utilized during the patient's clinical assessment or they were disregarded. In either case, the results would support or counter the physician's clinical decision for patient management. After predictive value analysis it was concluded that measurement of PSA alone is more useful than parallel measurements of PSA and PAP, when utilized together with standard criteria for assessing treated prostate cancer patients.     

Detection of prostatic cancer by solid-phase radioimmunoassay of serum prostatic acid phosphatase.

We compared our radioimmunoassay with the standard enzyme assay for prostatic acid phosphatase in the diagnosis of prostatic cancer. Serum samples from 50 controls, 113 patients with prostatic cancer, 36 with benign prostatic hyperplasia, 83 with other cancers, 20 with gastrointestinal disorders and 28 with total prostatectomies were randomized and studied by radioimmunoassay and enzyme assay. When the upper limit was set at 8.0 ng per milliliter (mean + 4 S.D.) the radioimmunoassay diagnosed prostatic cancer in 33, 79, 71 and 92 per cent of the patients with Stage I, II, III and IV disease. In contrast, the enzyme assay detected elevations of enzyme in the serum of 12, 15, 29, and 60 per cent respectively. No false-positive results were detected by either assay in normal controls but the radioimmunoassay test was positive in two patients with benign prostatic hyperplasia, in one patient after total prostatectomy, in nine with other cancers and in one of the group with gastrointestinal disorders. In contrast to the enzyme assay, the radioimmunoassay distinguished over half the cases of intracapsular prostatic cancer.     

Alteration of acid phosphatase isoenzyme in a human prostatic cancer cell line

The acid phosphatase (AcP) isoenzyme in a human prostatic cancer cell line was compared to that of prostatic tissue extract by electrophoresis. The major isoenzyme by prostatic tissue extract is the AcP isoenzyme 2, while only AcP isoenzyme 4 (AcP-4) was observed in the human prostatic cancer cell line. A monoclonal antibody specific to AcP-4 was used to investigate the ultrastructural distribution of AcP-4 in a prostatic cancer cell line. The peroxidase staining pattern indicates that AcP-4 is synthesized on bound ribosomes, discharged into the cisternae of rough endoplasmic reticulum, transported to the cisternae of Golgi apparatus for concentration and packaging, and transferred to the secretory vesicles for exocytosis. It is well known that synthesis and secretion of AcP-2 are the major characteristics of the highly differentiated prostatic epithelial cells. The present data demonstrate the loss of this specific function in the prostatic cancer cell line. Instead of AcP-2, the dedifferentiated cancer cell line synthesizes and secretes AcP-4, which is a common AcP isoenzyme of many nonprostatic tissues.     

A human prostatic bacterial isolate alters the prostatic microenvironment and accelerates prostate cancer progression

Inflammation is associated with several diseases of the prostate including benign enlargement and cancer, but a causal relationship has not been established. Our objective was to characterize the prostate inflammatory microenvironment after infection with a human prostate‐derived bacterial strain and to determine the effect of inflammation on prostate cancer progression. To this end, we mimicked typical human prostate infection with retrograde urethral instillation of CP1, a human prostatic isolate of Escherichia coli. CP1 bacteria were tropic for the accessory sex glands and induced acute inflammation in the prostate and seminal vesicles, with chronic inflammation lasting at least 1 year. Compared to controls, infection induced both acute and chronic inflammation with epithelial hyperplasia, stromal hyperplasia, and inflammatory cell infiltrates. In areas of inflammation, epithelial proliferation and hyperplasia often persist, despite decreased expression of androgen receptor (AR). Inflammatory cells in the prostates of CP1‐infected mice were characterized at 8 weeks post‐infection by flow cytometry, which showed an increase in macrophages and lymphocytes, particularly Th17 cells. Inflammation was additionally assessed in the context of carcinogenesis. Multiplex cytokine profiles of inflamed prostates showed that distinct inflammatory cytokines were expressed during prostate inflammation and cancer, with a subset of cytokines synergistically increased during concurrent inflammation and cancer. Furthermore, CP1 infection in the Hi‐Myc mouse model of prostate cancer accelerated the development of invasive prostate adenocarcinoma, with 70% more mice developing cancer by 4.5 months of age. This study provides direct evidence that prostate inflammation accelerates prostate cancer progression and gives insight into the microenvironment changes induced by inflammation that may accelerate tumour initiation or progression. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Immunodiagnosis by prostatic acid phosphatase to differentiate primary male breast cancer from metastatic prostate cancer

A patient who was treated with estrogens for carcinoma of the prostate was later diagnosed with apparent primary cancer of the male breast. He received chest-wall radiation therapy with curative intent. Later, immunodiagnosis by immunoperoxidase staining for human prostate-specific acid phosphatase of the breast tissue revealed that the patient actually had metastatic prostate cancer to the breast rather than primary breast cancer secondary to estrogen therapy. Use of highly specific peroxidase-antiperoxidase tissue staining for human prostate-specific acid phosphatase is recommended to differentiate primary male breast cancer from metastatic prostate cancer.     

Immunofluorescent localization of an androgen-dependent isoenzyme of prostatic acid phosphatase in rat ventral prostate

Isoenzymes of rat ventral prostate (RVP) acid phosphatase were isolated and partially purified by ultracentrifugation, Sephadex G-100 column chromatography, and isoelectric focusing. Antisera were raised to the isoenzymes of prostatic acid phosphatase by immunization of New Zealand white rabbits. Rabbit antisera reacting specifically to homologous but not heterologous isoenzymes of acid phosphatase were then reacted with a variety of tissues using indirect immunofluorescence. The tissues included prostate, spleen, bone marrow, liver, kidney, salivary gland complex, small intestine, and adrenal glands. An antiserum against a RVP acid phosphatase isoenzyme with a pI of 4.5 (A-PAP) localized acid phosphatase only in the supranuclear region of rat ventral prostate epithelial cells, and did not react with acid phosphatase in any of the other organs tested. A-PAP did not localize acid phosphatase in the ventral prostate from rats 14 days after castration. A-PAP did localize acid phosphatase in the ventral prostate from castrated animals that were treated with testosterone. These results indicate the A-PAP localized an androgen-dependent isoenzyme of acid phosphatase in RVP epithelial cells that may be secretory in nature. This antiserum should prove to be an ideal marker for studies involving hormonal regulation of prostatic epithelial function in vivo and in vitro.     

Epithelial markers in prostatic, bladder, and colorectal cancer: an immunoperoxidase study of epithelial membrane antigen, carcinoembryonic antigen, and prostatic acid phosphatase

Twenty prostatic adenocarcinomas, 20 transitional cell carcinomas of the bladder, and 20 colorectal adenocarcinomas were stained for epithelial membrane antigen, carcinoembryonic antigen, and prostatic acid phosphatase. Polyclonal affinity purified first and second antibodies and an indirect immunoperoxidase technique were used. All of the colorectal and bladder tumours and 16/20 prostatic tumours were positive for epithelial membrane antigen. All 20 colorectal, 7/20 bladder, and 5/20 prostatic tumours stained for carcinoembryonic antigen. All of the prostatic adenocarcinomas and none of the colorectal or bladder tumours were positive for prostatic acid phosphatase. These markers may be used to discriminate between tumours arising from these sites.     

Prostate cancer tends to metastasize in the bone-mimicking microenvironment via activating NF-kB signaling

Prostate cancer preferentially metastasizes to the bone. However, the underlying molecular mechanisms are still unclear. To explore the effects of a bone-mimicking microenvironment on PC3 prostate cancer cell growth and metastasis, we used osteoblast differentiation medium (ODM; minimal essential medium alpha supplemented with L-ascorbic acid) to mimic the bone microenvironment. PC3 cells grown in ODM underwent epithelial-mesenchymal transition and showed enhanced colony formation, migration, and invasion abilities compared to the cells grown in normal medium. PC3 cells grown in ODM showed enhanced metastasis when injected in mice. A screening of signaling pathways related to invasion and metastasis revealed that the NF-kB pathway was activated, which could be reversed by Bay 11-7082, a NF-kB pathway inhibitor. These results indicate that the cells in different culture conditions manifested significantly different biological behaviors and the NF-kB pathway is a potential therapeutic target for prostate cancer bone metastasis.     

An assessment of serum acid and alkaline phosphatase determinations in prostatic cancer with a clinical validation of an acid phosphatase assay utilizing adenosine 3′ -monophosphate as substrate

Serum acid phosphatase (AcPase) was measured by a colorimetric method utilizing adenosine 3' -monophosphate as substrate in 389 patients. In about half the cases blood was taken shortly after a rectal examination. The upper reference limit (mean + 2SD) for 116 cases with miscellaneous illness after eliminating outliers was 4.1 International Units per litre (U/I) at 37 degrees C, and no correlation existed between AcPase activity and age in these subjects (r = 0.040). Eight of 18 patients with untreated carcinoma confined within the prostate gland had AcPase activities below 4.1 U/l, and all of 27 cases with extension to pelvic soft tissues or to bone exceeded this value. AcPase activities above 4.1 U/l were found in 6% of cases with benign hypertrophy of the prostate, in 5% of cases with non-prostatic cancer, and in none of 22 cases with other urological illness.Raised serum alkaline phosphatase (APase) activity was found in 60% of patients with untreated prostatic cancer and in only 6% of patients free of prostatic cancer, in most of whom there was a clinical explanation for the elevation. The correlation between the two phosphatase activities was not significant (r = 0.294). While APase activity does not reflect the stage of the disease as closely as AcPase activity, and is not so frequently elevated, it provided useful confirmation of the diagnosis in five patients of the present series whose AcPase levels were normal or only minimally elevated.     

Immunohistochemical acid phosphatase level and tumor grade in prostatic carcinoma

An immunoperoxidase technique to detect prostatic-specific acid phosphatase (PSAP) was used on specimens from 98 cases of prostatic carcinoma that were graded by both the Gleason and the Mostofi systems, to see if tumor grade correlated with amount of PSAP seen in tissue. Most tumors showed strong, diffuse cytoplasmic staining; no significant difference was seen among the various grades. Other than focal, weak staining of renal tubular epithelium, the antibody to PSAP gave uniformly negative results with a variety of normal and neoplastic tissues. In light of the great sensitivity and specificity of this technique, it potential applications include diagnosis of poorly differentiated prostatic malignant neoplasms, whether primary or metastatic.     

Grossly elevated serum prostatic acid phosphatase in a patient with carcinoid

We report a case of carcinoid, diagnosed histochemically and biochemically, which was associated with grossly elevated serum prostatic acid phosphatase and normal serum prostate specific antigen.     

Purification of monoclonal antibodies raised against prostate-specific acid phosphatase for use in vivo in radioimaging of prostatic cancer

In developing diagnostic reagents for the radioimaging of prostatic cancer, methods were optimized for the purification of two mouse IgG1 monoclonal antibodies raised against prostate-specific acid phosphatase and produced in cell culture. Two different two-step methods were selected. One method consisted of two successive ion exchange chromatographic steps on Mono S and Mono Q; in the other method, Mono S chromatography was followed by hydrophobic interaction (Alkyl Superose) chromatography. In both cases, fast protein liquid chromatography (FPLC) instrumentation was used. The antibodies were purified from cell culture media containing fetal calf serum (1-5%). Highly pure (greater than 95%) IgG1 antibodies, free of contaminating serum-derived proteins or column materials, were obtained in good yield (greater than 90% recovery). The purified antibodies completely retained their immunological reactivity towards prostate-specific acid phosphatase and were sterile and pyrogen-free. Since the monoclonal antibodies produced were intended for applications in vivo, an essential feature of the methods selected was the availability of in situ cleaning procedures for sterilization of the gel materials and for the inactivation of viruses and pyrogens in the gels. The methods developed could be readily scaled up for preparative purposes.     

Tartrate-resistant acid phosphatase as a marker of bone metastases in patients with breast cancer and prostate cancer

Serum activity of tartrate-resistant acid phosphatase 5b (TRAP 5b) in patients with breast cancer and prostate cancer having bone metastases was much higher than in healthy donors and patients without skeletal injuries. TRAP 5b activity in patients with breast cancer and multiple bone metastases surpassed that in patients with single bone metastases. The mean activity of TRAP 5b and range of enzyme activity in women treated with bisphosphonates were significantly lower than in patients not receiving antiresorptive therapy. Diagnostic sensitivity and specificity of TRAP 5b as a marker of skeletal metastases in patients with breast cancer were 82 and 87%, respectively. In patients with prostate cancer these indexes were 71 and 83.4%, respectively. Detection of this marker in tumor patients holds much promise for early diagnostics of bone metastases, estimation of the severity of skeletal metastases, and monitoring of the efficiency of bisphosphonate therapy. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 7, pp. 91–93, July, 2004     

Tartrate-resistant acid phosphatase as a marker of bone metastases in patients with breast cancer and prostate cancer

Serum activity of tartrate-resistant acid phosphatase 5b (TRAP 5b) in patients with breast cancer and prostate cancer having bone metastases was much higher than in healthy donors and patients without skeletal injuries. TRAP 5b activity in patients with breast cancer and multiple bone metastases surpassed that in patients with single bone metastases. The mean activity of TRAP 5b and range of enzyme activity in women treated with bisphosphonates were significantly lower than in patients not receiving antiresorptive therapy. Diagnostic sensitivity and specificity of TRAP 5b as a marker of skeletal metastases in patients with breast cancer were 82 and 87%, respectively. In patients with prostate cancer these indexes were 71 and 83.4%, respectively. Detection of this marker in tumor patients holds much promise for early diagnostics of bone metastases, estimation of the severity of skeletal metastases, and monitoring of the efficiency of bisphosphonate therapy.