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An algorithm for prostate cancer detection in a patient population using prostate-specific antigen and prostate-specific antigen density.

Prostate-specific antigen (PSA) is the most accurate serum marker for cancer of the prostate (CaP). However, its sensitivity and specificity are suboptimal, especially at values ranging between 4.1 and 10.0 ng/ml (monoclonal), because benign prostatic hypertrophy and hyperplasia (BPH) and CaP frequently coexist in this range. This study was undertaken to determine the value of incorporating prostate volume measurements with serum PSA levels in a quotient (PSA/volume) entitled PSA density (PSAD). A total of 3140 patients were analyzed and stratified by serum PSA, digital rectal examination (DRE), transrectal prostate ultrasound (TRUS), TRUS volume determination and PSAD. All patients were referred for evaluation and therefore do not represent a screened population. Patients underwent prostate biopsies when abnormalities in TRUS or DRE were detected. Although both PSA and PSAD have statistical significance when the serum PSA value is < or = 4.0 ng/ml, neither has clinical significance in differentiating BPH from CaP. At serum levels ranging between 4.1 and 10.0 ng/ml, PSA has no ability to differentiate BPH from CaP, whereas PSAD does so with statistical and clinical significance. When the PSA value is between 10.1 and 20.0 ng/ml, only PSAD is statistically significant. When PSA exceeds 20 ng/ml, PSAD is redundant. We conclude that all patients with an abnormality on DRE or TRUS should undergo prostate biopsy. If the PSA value is < or = 4.0 ng/ml, TRUS and PSAD are not warranted and routine biopsy is not recommended. For intermediate PSA levels, 4.1-10.0 ng/ml, TRUS, TRUS prostate volume, and PSAD are important.2_

Aged

Sensitive detection of prostatic hematogenous tumor cell dissemination using prostate specific antigen and prostate specific membrane-derived primers in the polymerase chain reaction.

We developed a polymerase chain reaction based assay enabling sensitive detection of hematogenous tumor cell dissemination in patients with prostate cancer. We performed "nested polymerase chain reaction," amplifying messenger ribonucleic acid sequences unique to prostate specific antigen (PSA) and to the prostate specific membrane antigen, and compared the respective results. Prostatic tumor cells were detected in 2 of 30 patients (6.7%) by polymerase chain reaction with PSA derived primers, while prostate specific membrane primers detected tumor cells in 19 (63.3%). All 16 negative controls had negative PSA and prostate specific membrane polymerase chain reaction. Assays were repeated to confirm results, and polymerase chain reaction products were verified by deoxyribonucleic acid sequencing and Southern analysis. Patients harboring circulating prostatic tumor cells as detected by prostate specific membrane and not by PSA polymerase chain reaction included 7 of 13 previously treated by radical prostatectomy who had nonmeasurable serum PSA levels at the time of this assay. The significance of these findings with respect to future disease recurrence and progression will be investigated.

Base Sequence

The use of prostate specific antigen and prostate specific antigen density in the diagnosis of prostate cancer in a community based urology practice.

Since 1989 we have used serum prostate specific antigen (PSA) levels as an indication for ultrasound guided systematic biopsies of the prostate. Realizing that the PSA level in part reflects prostatic glandular epithelial volume, we reviewed the accumulated data on our last 2,340 biopsies to determine if the quotient of PSA and prostatic volume, prostate specific antigen density, provided any further diagnostic information. There were evaluable data for 2,020 patients. Prostate specific antigen density levels are shown to have a strong correlation with the diagnosis of prostate cancer and provide a more reliable indication for ultrasound guided biopsy of the prostate than PSA alone.

Adult

Effect of the addition of estrogen to medical castration on prostatic size, symptoms, histology and serum prostate specific antigen in 4 men with benign prostatic hypertrophy.

A total of 4 men with benign prostatic hypertrophy who underwent medical castration therapy with a long-acting gonadotropin-releasing hormone agonist (leuprolide) for more than 6 months elected to add an estrogen transdermal patch (0.05 mg. to the skin biweekly) to the leuprolide regimen. The average prostatic size (transrectal ultrasound), serum prostate specific antigen (PSA) levels and symptoms of prostatism were dramatically decreased with leuprolide alone. The addition of estrogen for 6 months did not result in any change in prostate size, symptoms or serum PSA levels over that seen with leuprolide alone. The development of squamous metaplasia was noted in 1 man with leuprolide alone and in 1 man after the addition of estrogen. Immunohistochemical staining with anticytokeratin 903 antibodies reveals that squamous metaplasia appears to arise from prostatic basal cells. We postulate that the target cell for estrogen action in the prostate is the prostatic basal cell. In the absence of androgen the only direct effect of estrogens is the induction of squamous metaplasia.

Aged

Argyrophilic prostatic carcinoma. Case report with literature review on prostatic carcinoid and "carcinoid-like" prostatic carcinoma.

An unusual prostatic neoplasm characterized by a carcinoid-like light microscopic pattern together with argyrophilia of tumor cells is described. Immunoperoxidase stain for prostatic specific antigen, however, was positive, indicating that this neoplasm was an argyrophilic prostatic carcinoma. Although the clinical significance of a carcinoid-like pattern and/or argyrophilia in prostatic carcinoma is currently unknown, pathologic recognition of these features is of paramount importance because prostatic carcinoma with these features has to be distinguished from true primary prostatic carcinoid tumor or, in areas of metastasis, from metastatic carcinoid originating from other sites such as the gastrointestinal or respiratory tracts. The value of the immunoperoxidase technique for prostatic specific antigen as well as prostatic acid phosphatase in this differentiation is stressed.

Adenocarcinoma

Characteristics of prostatic infarcts and their effect on serum prostate-specific antigen and prostatic acid phosphatase.

OBJECTIVES: To determine how prostatic infarcts affect serum prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) levels. METHODS: Two hundred eighteen clinically benign, whole prostates were obtained at autopsy, completely sectioned, and examined histologically. PSA and PAP levels were determined from premortem serum. RESULTS: Six of the 218 (2.8%) prostates had infarcts. The infarcts were usually multiple and usually located in the central and/or middle concentric zones of the middle third of the prostate without a preference for a particular lobe. Serum PSA by immunoradiometric assay were elevated in all 6 cases. Serum PAP by both enzymatic assay (ACA), and immunoradiometric assay were available for 5 cases and were elevated by both methods in 2 cases, approached elevated levels by both methods in 1 case, and were normal by both methods in 2 cases. The PSA and PAP levels appeared to be affected more by the age than by the size of the infarct. CONCLUSIONS: Prostatic infarcts elevate PSA levels more frequently than PAP levels, and prostatic infarcts may be responsible for some unexplained elevations of serum PSA and PAP levels.

Acid Phosphatase

Correlation of prostate-specific acid phosphatase and prostate-specific antigen immunocytochemistry with survival in prostate carcinoma.

Prostate-specific acid phosphatase, a secretory product of prostatic cells, may be a secondary product of the interaction of hormones with their receptor proteins. In this study we have examined two independent patient populations to see whether the intensity or extent of prostate-specific acid phosphatase and/or prostate-specific antigen staining correlated with survival and hormonal manipulation. One population of 24 patients was selected from patients undergoing surgical resection for adenocarcinoma Stage B or C at the Mayo Clinic. The second population of 123 patients was obtained from Radiation Therapy Oncology Group Protocols 75-06 and 77-06. Tissue from both populations was analyzed. In both populations, the intensity of prostate-specific acid phosphatase staining correlated with survival in a statistically significant manner. Staining with prostate-specific antigen was present in greater than 90% of specimens; data was therefore not analyzed. In those patients who subsequently relapsed and were subjected to hormonal manipulation, there appeared to be a higher likelihood of response to hormones with intense prostate-specific acid phosphatase staining.

Acid Phosphatase

Enzyme immunoassay of prostatic acid phosphatase after prostatic examination. Correlation with prostate size and immunopathology.

Variation in serum prostatic acid phosphatase (PAP) after prostatic digital examination was studied in 22 patients, 18 with benign prostatic hyperplasia (BPH), and 4 with prostatic carcinoma. Serum PAP was determined by enzyme immunoassay (EIA) and compared with standard enzymatic assay (EA). Prostatic tissue from transurethral resection (TUR) was subjected to routine pathologic examination and stained for PAP. PAP level increased above reference range and up to several-fold in 12 of 22 patients (54.5%) by EIA and in 22.7 percent by EA. The increase in PAP correlated positively with the prostate size estimated by digital palpation (R = 0.82, P less than 0.001). There was no definite correlation between the histologic parameters studied and the increase in PAP. No day-to-day variation in PAP level was detected in 8 other patients when samples were taken at 7 AM for three successive days. For proper comparison of PAP value, we suggest that sampling time should be fixed and specimens should be taken before prostatic manipulation.

Acid Phosphatase

Adenoid cystic carcinoma of the prostate. A case report with immunoperoxidase staining for prostate-specific acid phosphatase and prostate-specific antigen.

Adenoid cystic carcinoma occurs most commonly in the major and minor salivary glands, but also has been recognized in numerous other locations. Adenoid cystic carcinoma of the prostate gland is, however, extremely uncommon with only two other reported cases. The authors have studied a case of adenoid cystic carcinoma of the prostate with immunoperoxidase staining for both prostate-specific acid phosphatase and prostate-specific antigen, which have been shown to be specific for normal prostatic epithelium and prostatic carcinoma. The negative staining for these antigens in this tumor distinguishes adenoid cystic carcinoma from the usual acinic adenocarcinomas of the prostate, and suggests an origin from periurethral glands or metaplastic urethral mucosa.

Acid Phosphatase

[Prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostate specific antigen (PA) in prostatic cancer].

The levels of prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostate specific antigen (PA) were determined in the serum of 200 untreated patients 28 patients with reactivated prostatic cancer and 179 patients with benign prostatic hypertrophy (BPH) from 1979 to 1987. PAP and gamma-Sm were determined using an Eiken and Chugai kit, respectively and PA was assayed using an Eiken or Travenol kit. The sensitivity of PAP, gamma-Sm and PA respectively in the untreated prostatic cancer cases was 0, 0% and 67%, for Stage A1, 25, 17 and 100% for Stage A2, 23, 50 and 60% for Stage B, 62, 81 and 94% in Stage C, 58, 67 and 90% for Stage D1, 86, 88 and 100% for Stage D2. The specificity of PAP, gamma-Sm and PA is 89, 69 and 43%, respectively. The efficiency of PAP was the highest at all stages as a whole, but when compared at each stage, gamma-Sm was the highest at Stages B and C. The sensitivity of simultaneous assays of PAP and gamma-Sm was slightly increased, but sensitivity was not increased by simultaneous use of three markers. The efficiency of a simultaneous assay was lower than that of a single assay with PAP. However, combined determination of gamma-Sm or PA with PAP was found to be useful for monitoring the clinical course of the reactivated patients. Correlation between PAP and PA levels was high, but that between gamma-Sm and PA levels was low. There was no correlation between PAP and gamma-Sm levels. In conclusion, PAP is the most valuable marker for prostatic cancer, and gamma-Sm is of value for use in combination with PAP. However, an additional PA assay was not found to be of advantage.

Acid Phosphatase

Primary prostatic carcinoid tumor with intracytoplasmic prostatic acid phosphatase and prostate-specific antigen.

A case of prostatic carcinoid tumor with lymph node metastases is reported. The patient was a 78-year-old male who died in ventricular fibrillation. At autopsy, a 2 X 2 cm, white, irregular tumor was found in the prostate and there were several enlarged para-aortic lymph nodes. Both specimens contained a characteristic carcinoid tumor. Argyrophil stains revealed strong positivity in the primary as well as in the metastatic tumors. Electron micrographs prepared from formalin-fixed tissue demonstrated numerous membrane-bound dense-core granules. Immunoperoxidase-labeled antibodies against both prostatic acid phosphatase and prostate-specific antigen localized in the tumor cells. The ultrastructural and immunohistochemical results support differentiation of the tumor cells toward both prostatic epithelial cells and endocrine cells. We believe that this is the first reported case of a prostatic carcinoid tumor in which specific prostatic tissue markers have been demonstrated in the tumor cells.

Acid Phosphatase

Tissue concentrations of prostate-specific antigen in prostatic carcinoma and benign prostatic hyperplasia.

Prostate-specific antigen (PSA), as measured in peripheral blood, is currently the most widely used marker for the assessment of tumor burden in the longitudinal study of patients with carcinoma of the prostate (PCA). Studies from other laboratories have led to the conclusion that a given volume of PCA causes a much higher level of PSA in the peripheral circulation of patients than a similar volume of prostate without carcinoma. We have evaluated PSA in the resected tissues immunohistochemically and in extracts of PCA and of prostates resected because of benign prostatic hyperplasia (BPH) with an enzyme-linked immunosorbent assay. Immunohistochemical results were less quantitative than but consistent with the results of the ELISA of tissue extracts. Immunohistochemically, there was considerable heterogeneity in the expression of PSA by both PCA and BPH both within and among prostatic tissues from different patients. While the levels of expression of PSA in these tissues overlap broadly, PSA is expressed at a lower level in PCA than in BPH when PSA is expressed as a function of wet weight of tissue (p = 0.0095), wet weight of tissue/% epithelium (p less than 0.0001), protein extracted from the tissue (p = 0.0039), or protein extracted/% epithelium (p less than 0.0001).

Adult

Excretion of three major prostatic secretory proteins in the urine of normal men and patients with benign prostatic hypertrophy or prostate cancer.

We have studied the mode of excretion of three prostatic secretory proteins, namely acid phosphatase (PAP), prostate-specific antigen (PSA) and beta-inhibin, in the urine of normal adult men, and we have determined the urinary levels of these proteins in men with benign prostatic hypertrophy (BPH) or adenocarcinoma. The output of the three proteins was highly variable during the day. In order to minimize these variations, 24-hour urine samples were collected thereafter. Our study showed that PAP concentrations in 50% of men with or without symptomatic BPH were similar to those of normal young men. In the remaining 50%, PAP was undetectable. In contrast, average PSA and beta-inhibin concentrations were higher in patients with BPH than in young men (p less than 0.05). The three markers were decreased or nondetectable in about half of the patients with untreated prostatic cancer. This phenomenon was even more pronounced in patients receiving hormonal treatment (castration or diethylstilbestrol). However, some of these patients still excreted normal amounts of PAP, PSA, and beta-inhibin. Urinary and serum PAP levels showed no correlation. These results indicate that urinary prostatic markers provide an easy means to study the behavior of the primary prostatic tumor. This information may be of potential value since it is not obtained with serum markers which originate mostly from metastatic cells.

Acid Phosphatase

The diagnostic value of urinary transferrin compared to serum prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) in patients with prostatic cancer.

Urinary transferrin, serum prostatic acid phosphatase (PAP) and prostatic-specific antigen (PSA) concentrations were measured in patients with prostatic cancer, prostatitis, benign prostatic hypertrophy (BPH) and in a control group. In contrast to recently published data it is concluded that urinary transferrin is not suitable as a tumor marker for prostatic carcinoma. Receiver Operating Characteristic curves were constructed to compare the diagnostic value of the different tests at different cutoff values. Sensitivity and specificity of the urinary marker are extremely low compared to the serum markers PAP and especially PSA, making the former not suitable as an additional marker.

Acid Phosphatase

Inter-relation between measurement of serum prostatic specific antigen and transrectal ultrasound in the diagnosis of benign prostatic hyperplasia and prostatic cancer.

Serum prostatic specific antigen (PSA) and ultrasound-determined prostatic volume (UPV) were measured in 50 patients with histologically proven benign prostatic hyperplasia (BPH) and in 40 patients with histologically proven prostatic cancer of whom 17 had evidence of distant metastases (M1) and 23 did not (M0). A good correlation between log PSA and UPV was demonstrated in the BPH group and rearrangement of the linear regression equation allowed calculation of a single variable--the log PSA corrected to a standard prostate volume for any given individual. A volume-corrected PSA correctly identified all patients with M1 disease and greatly improved but did not eliminate overlap of M0 disease with BPH. Reduction of serum PSA to a single volume-corrected variable will allow the introduction of practical and optimum protocols for the management of patients with prostatic enlargement.

Aged

Clinical usefulness of prostate-specific antigen and prostatic acid phosphatase in patients with prostatic cancer.

Serum prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) levels were measured in 70 patients with benign prostatic hypertrophy (BPH) and in 70 patients with prostatic cancer. PSA was increased above the cutoff level of 10 ng/ml in 13% of patients with BPH and in 87% of patients with prostatic cancer. In contrast, abnormal PAP levels were found in 14 and 76% of patients, respectively. We concluded that, due to its high specificity, PSA is a useful marker in the management of patients with prostatic carcinoma and that it surpasses PAP in this regard.

Acid Phosphatase

[The correlation between the level of prostate-specific antigen and prostate gland volume in the early diagnosis of prostatic cancer].

One hundred and eighty six patients (Pts) presenting with either an abnormal per rectum examination (P.R. suggestive of prostatic cancer (P.Ca) (excluding stage T3) or a prostatic specific antigen (P.S.A.) level greater than or equal to 2.5 ng/ml (radioimmunoassay) were submitted to transrectal ultrasonography (T.R.U.) using a 7 MHz transducer. The prostatic volume (Vol.P) was systematically calculated during T.R.U. and correlated with the P.S.A. level. Six systematic multiple ultrasound-guided biopsies (S.M.U.B.) were performed in the 2 prostatic lobes (3 per lobe) regardless of the result of T.R.U. In the 111 patients in whom the S.M.U.B. were negative, a highly significant correlation (p < 0.001) was observed between the serum P.S.A. level (y) and the prostatic volume (Vol.P): y = (4.13 +/- 0.15 Vol.P) +/- 8.43. In the 75 Pts with P.Ca, the P.S.A./Vol.P correlation was significantly different (p < 0.05) from the straight line of regression with the previous standard deviation. A similar difference in correlation (p < 0.05) was observed in the sub-group of 14 Pts with P.Ca despite normal P.R. and T.R.U. These results suggest: 1) that there is a correlation between the Vol.P measured by T.R.U. and the P.S.A. level in patients with negative S.M.U.B. 2) that the absence of correlation is highly suspicious of P.Ca and requires S.M.U.B. 3) that there is a 15% incidence of P.Ca in the sub-group of Pts with normal P.R. and T.R.U. which are only detected by the raised P.S.A. not correlated with the volume of the prostate.

Biopsy

Impact of prostate size on the outcome of transurethral laser evaporation of the prostate for benign prostatic hyperplasia.

OBJECTIVES: The aim of this study was to evaluate efficacy and safety of transurethral evaporation of the prostate (TUEP) using neodymium:yttrium-aluminum-garnet (Nd:YAG) laser in prostate glands of various sizes. METHODS: One hundred consecutive patients with benign prostatic hyperplasia (BPH) and prostate volumes less than 40 cc (group I, n = 41), 41 to 80 cc (group II, n = 39), and more than 80 cc (group III, n = 20), who had preoperative prostate volume estimation by transrectal ultrasound and had completed a minimum of 3 months' follow-up, underwent TUEP. At baseline, and at 3 and 6 months, American Urological Association (AUA) score, peak flow rate (PFR), postvoid residual urine (PVR), and complications, if any, were documented. RESULTS: There were no significant differences in failure rates, complications, or ability to improve symptom score, PFR, and PVR between patients with prostate glands of various sizes. The mean improvement in PFR at 6 months was: group I, 9.9 cc/s (116%); group II, 7.4 cc/s (81%); and group III, 9.2 cc/s (107%). Reduction in AUA score was: group I, 14.6 (63%); group II, 17.7 (71%); and group III, 16.2 (70%). PVR was: group I, 62.5 cc (51%); group II, 31.4 cc (16%), and group III, 71 cc (83%) (differences not significant). The patients in urinary retention were separately analyzed (group I, 9, group II, 12, and group III, 5) and mean PFR at 6 months was: group I, 18.5 cc/s, group II, 15 cc/s, and group III, 17.1 cc/s. Mean AUA score at 6 months was: group I, 25.8; group II, 21; and group III, 23.6. Mean PVR score was: group I, 370 cc, group II, 439 cc; and group III, 400 cc (differences not significant). Mean postoperative catheterization time was higher in patients with glands larger than 80 cc (2.2 versus 2.9 versus 4.7 days in groups I, II, and III, respectively, P < 0.009 between groups II and III). Incidence of urinary tract infection (10 versus 0%) was greater in patients receiving only 48-hour as opposed to 10-day postoperative antibiotics. CONCLUSIONS: TUEP appears to be a safe and effective treatment for relief of symptoms of BPH and improvement of PFR in patients with all sizes of prostate glands.

Aged