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PubMed1999

Western blotting analysis of antibodies to prostate-specific antigen: specificities for prostate-specific antigen and prostate-specific antigen fragments.

Approximately 40% of the prostate-specific antigen (PSA) purified from seminal fluid comprises cleaved or fragmented forms of PSA. These fragments are observed by reduced SDS-PAGE and have been identified in preparations of purified seminal plasma. The comparative analysis of 53 antibodies, submitted to an international PSA Workshop, with different PSA variants was studied using SDS-PAGE and Western blotting. Six different patterns of reactivity were observed which may reflect different epitopes recognized by this panel of antibodies. Additional antibody studies to nonreduced intact PSA suggest the epitopes are conformation-dependent.

Antibody Specificity↗
PubMed1990

[Clinical studies on chronic prostatitis and prostatitis-like syndrome. (3). Clinical re-examination of chronic bacterial prostatitis using the criteria for clinical evaluation].

In accordance with the criteria for clinical evaluation, established by the UTI research group, 43 cases of chronic bacterial prostatitis were retrospectively analyzed. The subjective symptoms were "resolved" in 18.5%, "improved" in 46.5%, and "persisted" in 34.9%. The white blood cells were "cleared" in 34.9%, "decreased" in 37.2%, and "unchanged" in 27.9%. The bacteria were "eliminated" in 51.2%, "decreased" in 16.2%, "replaced" in 11.6%, and "unchanged" in 21.0%. Overall clinical efficacy was "excellent" in 51.2%, "moderate" in 39.5%, and "poor" in 27.9%, with an overall effectiveness rate of 72.1%. Bacteria (isolated bacteria: 8 species, 52 strains) were "eradicated" in 69.2% (GNR 71.4%, GPC 66.7%), and "persisted" in 30.8%. The bacterial eradication rate was 87.5% for E. coli, 58.3% for S. epidermidis, and 75.0% for E. faecalis. The analytical results of the clinical effects, classified by characteristic factor, showed significantly better results, in the excellence rate (p less than 0.05) and the overall effectiveness rate (p less than 0.01) of primary cases as compared with relapse cases. Among the isolated bacterial species, GNR showed more favorable results in comparison with GPC but without any significant difference. Further, the results of 81.3% for E. coli, 66.7% for S. epidermidis, and 62.5% for E. faecalis, indicates no significant difference between respective bacterial species. The new quinolones showed a favorable rate of 92%, followed by 80% of ST (sulfamethoxazole-trimethoprim), and 78% of tetracyclines, with a significant difference (p less than 0.01) in comparison with the mean overall effectiveness rates of cephems, penicillins, and old quinolones.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Quinolones↗
PubMed1989

Clinical use of prostate specific antigen in patients with prostate cancer.

The clinical use of prostate specific antigen as a screening test for prostate cancer, as a preoperative determinant for staging of prostate cancer and to monitor response to therapy in prostatic cancer patients was evaluated in 168 men with benign prostatic hyperplasia and 231 men with prostate cancer. Only 3% of the men with benign prostatic hyperplasia had prostate specific antigen levels greater than 10 ng. per ml. compared to 44% of the men with proved prostate cancer. Preoperative prostate specific antigen levels increased with higher clinical stages of prostate cancer but there was substantial overlap among stages. Among patients with stage A1 prostate cancer who were followed expectantly none had an elevated prostate specific antigen value or metastatic disease during a followup of 15 to 120 months. After radical prostatectomy serum prostate specific antigen values decreased to undetectable levels (less than 0.6 ng. per ml.) in 89% of the patients with organ-confined disease, in 87% of those with microscopically positive margins only but in only 34% with seminal vesicles or lymph node involvement. Failure of the prostate specific antigen levels to decrease to the undetectable range after radical prostatectomy was associated with a greater likelihood of subsequent tumor recurrence. Only 3 of 18 patients (17%) treated with definitive radiation therapy had post-irradiation prostate specific antigen values of less than 0.6 ng. per ml., while in 39% the prostate specific antigens values remained greater than 4 ng. per ml. and in 4 of 18 (22%) the values were greater than 10 ng. per ml. Of patients with previously untreated stage D2 prostate cancer the mean pre-treatment prostate specific antigen value was 63.7 ng. per ml. compared to a post-hormonal therapy mean value of 31.1 ng. per ml. Of 32 patients treated with hormonal therapy 14 had stable disease, including 13 with prostate specific antigen levels of less than 10 ng. per ml. In contrast, 18 patients had progressive disease, of whom 16 had prostate specific antigen levels of more than 10 ng. per ml. We conclude that the serum prostate specific antigen assay is most useful clinically to monitor the response to therapy of prostate cancer patients.

Acid Phosphatase↗
PubMed1989

The influence of reversible androgen deprivation on serum prostate-specific antigen levels in men with benign prostatic hyperplasia.

This study was designed to investigate the relationship of serum prostate-specific antigen to prostatic size and hormonal stimulation. Seven patients with benign prostatic hyperplasia were treated for six months with nafarelin acetate and then followed for an additional six months. Nafarelin acetate is a potent luteinizing-hormone-releasing hormone agonist which causes reversible testosterone deprivation resulting in involution of the prostate. During therapy and follow up, serum prostate-specific antigen correlated with: 1) serum testosterone (p less than 0.001); 2) quantity of prostatic epithelium (p less than 0.001); and 3) prostatic size (p less than 0.05). Before therapy, serum prostate-specific antigen (mean +/- SD) was 0.43 +/- 0.2 ng./ml. per gram of epithelium. This did not change significantly after six months of androgen deprivation (0.48 +/- 0.36), although the ratios of prostate-specific antigen to testosterone and to prostatic size each changed significantly. Despite testosterone levels in the castrate range at six months, five of seven patients had serum prostate-specific antigen concentrations above the female range and three of seven patients had prostatic biopsies containing columnar epithelium which stained positively for prostate-specific antigen. These results demonstrate that serum prostate-specific antigen is related to prostatic size, prostatic epithelial weight, and testosterone stimulation. However, prostatic size is not a good predictor of serum prostate-specific antigen because there is tremendous variation in the relative amount of epithelium in a prostate; in this study the ratio of prostatic size to epithelial weight varied threefold. Furthermore, although testosterone determines prostatic size and amount of prostatic epithelium, it may not totally control prostate-specific antigen production.

Aged↗
PubMed2007

Prostate specific antigen density correlates with features of prostate cancer aggressiveness.

PURPOSE: An increased prostate specific antigen density (serum prostate specific antigen divided by prostate volume) is an established parameter to help determine the need to perform prostate biopsies. A man with a high prostate specific antigen and a normal size prostate gland is more likely to have cancer than a man with the same prostate specific antigen and a large gland. Prostate specific antigen in relation to prostate size should also reflect the volume of cancer in the gland. One group defined clinically unimportant prostate cancer as tumor volume less than 0.5 cc, organ confined disease and Gleason less than 7. Another group noted that at the time of biopsy, a prostate specific antigen density less than 0.15 ng/ml/cc combined with low risk clinical tumor features predicted insignificant cancer. There are limited published validating data on the association of prostate specific antigen density with the criteria for prostate cancer aggressiveness. We tested the association of prostate specific antigen density with features of tumor aggressiveness in a screened and in a nonscreened cohort of patients with clinically localized prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: The screened patient cohort included 1,280 patients with screen detected prostate cancer treated from 1990 to 2002 at Washington University, and the nonscreened cohort included 382 patients treated from 2003 to 2004 at Northwestern University. We recorded the clinical and pathological tumor parameters in a prospective database. Parameters evaluated were pathological tumor stage, Gleason sum, tumor volume, biochemical progression and the previously mentioned 2 criteria for clinically unimportant cancers. We grouped patients into 4 prostate specific antigen density categories of less than 0.1, 0.1 to 0.14, 0.15 to 0.19 and greater than 0.19 ng/ml/cc. RESULTS: There was a significant trend for worsening clinicopathological prognostic features as prostate specific antigen density increased. There were 357 (82%), 283 (75%), 171 (75%) and 192 (55%) men with organ confined disease with clear surgical margins if prostate specific antigen density was less than 0.1, 0.1 to 0.14, 0.15 to 0.19 and greater than 0.19 ng/ml/cc, respectively (p <0.001). There were 86 (20%), 102 (27%), 64 (28%) and 157 (45%) men with a Gleason sum greater than 7 when grouped into each increasing PSA density category, respectively (p <0.001). There were 91 (21%), 91 (25%), 74 (33%) and 157 (46%) men with a total cancer volume greater than 0.5 cc when grouped into each increasing PSA density category, respectively (p <0.001). Prostate specific antigen velocity was greater than 2 ng/ml per year in 11%, 30%, 27% and 46% of men if prostate specific antigen density was less than 0.1, 0.1 to 0.14, 0.15 to 0.19 and greater than 0.19 ng/ml/cc, respectively (p <0.001). CONCLUSIONS: Prostate specific antigen density measurements are useful in helping to determine the aggressiveness of clinically localized prostate cancer, and can be used as an adjunct in predicting insignificant cancer and outcomes after local therapy.

Aged↗
PubMed2004

The use of real-time reverse transcription-PCR for prostate-specific antigen mRNA to discriminate between blood samples from healthy volunteers and from patients with metastatic prostate cancer.

PURPOSE: A clinical role for nonquantitative reverse transcription-PCR (RT-PCR) using prostate-specific antigen in blood samples from patients with prostate cancer remains undefined. Assay variation and detection of prostate-specific antigen mRNA illegitimate transcription may explain inconsistent results between studies. Defining levels of prostate-specific antigen mRNA expression in blood samples from healthy volunteers and patients with prostate cancer would allow cutoffs to be established to distinguish the two groups. EXPERIMENTAL DESIGN: Quantitative real-time RT-PCR for prostate-specific antigen mRNA was established and levels of prostate-specific antigen mRNA measured in bloods samples from healthy volunteers (n=21) and patients with localized (n=27) and metastatic (n=40) prostate cancer. RESULTS: Levels of prostate-specific antigen mRNA were significantly higher in blood samples from patients with metastatic prostate cancer than in blood samples from patients with localized prostate cancer (P <0.001) or in blood samples from healthy volunteers (P <0.01); levels between patients with localized prostate cancer and healthy volunteers were no different. Assay sensitivity to detect patients with metastatic prostate cancer was 68% with specificity of 95%. In patients with newly diagnosed metastatic prostate cancer, monitoring response to hormonal therapy was possible with this assay. No correlation between levels of prostate-specific antigen mRNA and serum prostate-specific antigen protein levels was found, suggesting that prostate-specific antigen mRNA and serum prostate-specific antigen protein levels reflect different features of prostate cancer, i.e., circulating tumor cells and total tumor bulk, respectively. CONCLUSIONS: Quantitative RT-PCR discriminates patients with metastatic prostate cancer from healthy volunteers and patients with localized prostate cancer but cannot discriminate patients with localized prostate cancer from healthy volunteers. A role for quantitative RT-PCR has been identified in the assessment and monitoring of patients with metastatic prostate cancer.

Cell Line, Tumor↗
PubMedDate not supplied

Tissue expression of neu differentiation factor/heregulin and its receptor complex in prostate cancer and its biologic effects on prostate cancer cells in vitro.

BACKGROUND: Prostate cancer is the most common cancer in American men and the second leading cause of cancer death. All clinical observations correlate poorly differentiated high-grade prostate cancer with disease-specific mortality. The HER2 cell membrane tyrosine kinase, a member of the epidermal growth factor receptor family that is the transcription product of the erbB2neu oncogene, and HER3, a receptor protein of the same family, are overexpressed in prostate cancer and prostatic intraepithelial neoplasia. The ligand for these receptors and another related family member, HER4, has recently been identified by independent investigator groups and called neu differentiation factor (NDF) or heregulin. In vitro treatment of HER2- and HER3- or HER2- and HER4-expressing breast cancer cells stimulates tyrosine phosphorylation of HER2 and produces changes in the rate of proliferation, degree of cellular differentiation, and synthesis of physiologic secretion products. There are no published reports on the expression of NDF and HER4 in prostate cancer or the in vitro effects of NDF in prostate cancer cells. METHODS: Expression of NDF, HER2, HER3, and HER4 was studied in 24 frozen prostatectomy specimens by immunohistochemistry. The biologic effect of human recombinant NDF was studied in vitro, using the LNCaP, PC3, and DU145 human prostate cancer cell lines. HER and NDF protein expression was studied by immunohistochemistry. NDF mRNA was analyzed using reverse transcriptase polymerase chain reaction from whole RNA. The biologic effects of NDF on prostate cancer cells in vitro included cell proliferation, thymidine synthesis, induction of prostate-specific antigen mRNA, anchorage-dependent and anchorage-independent cell growth, and ploidy analysis. Data analysis was performed using Student's t test. RESULTS: Observations in clinical prostatectomy specimens: Immunohistochemistry studies in clinical prostatectomy specimens demonstrate absence of significant NDF expression in prostate cancer, whereas it is expressed in 100% of the stroma, 100% of basal epithelial cells, and 58% of luminal cells in normal and benign hyperplastic prostatic tissue. The HER4 receptor protein is strongly expressed by normal prostate luminal cells, but not prostate cancer. Benign prostate tissue exhibits strong expression of HER2, HER3, and HER4 by basal cells, but only luminal cells significantly express HER4. Only 23% of prostate cancer specimens express HER4, while 95% express HER3 and 82% HER2. Prostatic intraepithelial neoplasia stained similarly to cancer for all proteins studied. Observations in prostate cancer cell lines: In vitro treatment with NDF significantly reduces aneuploidy and proliferation and growth of androgen-sensitive prostate cancer cells. Incubation with NDF also induces prostate-specific antigen mRNA in prostate cancer cells. In spite of displaying NDF mRNA, prostate cancer cells do not produce detectable NDF protein, but express HER2 and HER3 proteins. DISCUSSION: These data suggest that NDF may be a paracrine differentiation factor involved in normal adult prostate physiology and that functional loss of the NDF/HER ligand/ receptor loop may be an early event associated with prostate tumorigenesis.

Antineoplastic Agents↗
PubMed1999

The effect of high grade prostatic intraepithelial neoplasia on serum total and percentage of free prostate specific antigen levels.

PURPOSE: It is established that the percentage of free prostate specific antigen (PSA) in serum is low in patients with prostate cancer. An unanswered question is whether a low percentage of free PSA can be explained by high grade prostatic intraepithelial neoplasia alone. We compared the percentage of free PSA in men with high grade prostatic intraepithelial neoplasia alone, prostate cancer, benign prostatic hyperplasia (BPH) and a normal prostate (that is normal digital rectal examination and PSA less than or equal to 2.5 ng./ml.). MATERIALS AND METHODS: From October 1994 through December 1997, 48 men were diagnosed with high grade prostatic intraepithelial neoplasia without concomitant prostate cancer. Of these men 43 with a mean age plus or minus standard deviation of 67.4 +/- 7.8 years comprised our study group. To date none has been diagnosed with cancer during followup. Serum free and total PSA levels were measured, and the percentage of free PSA was calculated. The percentage of free PSA in the 43 men was compared to that in 50 with prostate cancer (mean age 65.4 +/- 7.8 years), 50 with biopsy proved BPH (67 +/- 7) and 43 with a normal prostate (61 +/- 8). RESULTS: There was no significant difference in mean total serum PSA in patients with high grade prostatic intraepithelial neoplasia, prostate cancer or BPH. The percentage of free PSA was significantly lower in patients with prostate cancer (14.9 +/- 6.5%) than those with high grade prostatic intraepithelial neoplasia (20.8 +/- 7.1%), BPH (20.1 +/- 7.3%) or a normal prostate (27.7 +/- 12.2%). There was also no significant difference in the percentage of free PSA between men with high grade prostatic intraepithelial neoplasia (20.8 +/- 7.1%) and those with BPH (20.1 +/- 7.3%). Additionally, men with a normal prostate had a higher percentage of free PSA (27.7%) than those with BPH (20.1%), high grade prostatic intraepithelial neoplasia (20.8%) or prostate cancer (14.9%). CONCLUSIONS: The percentages of free PSA in men with high grade prostatic intraepithelial neoplasia and BPH are similar, and significantly higher than those found in men with prostate cancer.

Aged↗
PubMed2004

Incidence and location of prostate and urothelial carcinoma in prostates from cystoprostatectomies: implications for possible apical sparing surgery.

PURPOSE: Prostatic carcinoma (Pca) at cystoprostatectomy is usually an incidental finding with the majority thought to be clinically insignificant. Most studies have not specifically addressed the location of Pca or the incidence and location of in situ or invasive urothelial carcinoma (Uca) in prostates of cystoprostatectomy specimens. The frequency of involvement of the apex with these processes has clinical implications. Specifically urinary continence following orthotopic diversion may be enhanced by prostate apical sparing. In this study the pathological features of Pca and Uca, and the frequency of apical involvement were investigated in prostates from cystoprostatectomy specimens. MATERIALS AND METHODS: Whole mounted prostates from 121 consecutive cystoprostatectomy specimens were analyzed. Pca location, tumor volume, grade, stage, surgical margin and pelvic lymph node status of Pcas were assessed. Clinically insignificant Pcas had a volume of less than 0.5 cc without Gleason pattern 4, extracapsular extension, seminal vesicle invasion, lymph node involvement or positive surgical margins. Prostate involvement by Uca or urothelial carcinoma in situ (CIS)/severe dysplasia and its location were assessed. RESULTS: Of 121 prostates 50 (41%) had unsuspected Pca, of which 24 (48%) were clinically significant. Of Pcas 30 of 50 (60%) involved the apex, including 19 of 24 (79%) that were significant and 11 of 26 (42%) that were insignificant. Of 121 prostates 58 (48%) had Uca involving the prostatic stroma, noninvasive Uca or urothelial CIS/severe dysplasia in the prostatic urethra or periurethral ducts, of which 19 (33%) had apical involvement. Overall only 32 of 121 patients (26%) had no Pca or prostate Uca/CIS and only 45 (37%) had no clinically significant Pca or Uca/CIS in the prostate. However, 74 of the 121 patients (61%) had no prostatic apical involvement by Pca or Uca/CIS and 85 (70%) had no apical involvement by clinically significant Pca or Uca/CIS. Patients with prostatic apical involvement by invasive or in situ Uca uniformly had involvement of more proximal (toward the base) portions of the prostate. CONCLUSIONS: The majority of prostates from cystoprostatectomies had no involvement of the prostatic apex by Uca or clinically significant Pca. Hence, most patients may be candidates for prostate apical sparing. However, involvement of the apex by Uca in any patient raises concern about procedures that leave portions of the prostate urethra after cystectomy in an effort to improve continence. In candidates for orthotopic neobladder reconstruction removing all of the prostatic urethra and sparing the remainder of the prostatic apex may allow improved preservation of urinary continence with an acceptable low risk of clinical Pca progression. Whether future strategies for preoperative exclusion of apical Pca and intraoperative assessment of more proximal prostate to help exclude apical urothelial disease may identify patients suitable for prostatic apical sparing remains to be determined. The impact on functional outcomes and cancer control also require additional study.

Adult↗
PubMed2006

A prospective, randomized trial comparing conventional transurethral prostate resection with PlasmaKinetic vaporization of the prostate: physiological changes, early complications and long-term followup.

PURPOSE: We compared standard transurethral prostate resection with bipolar PlasmaKinetic prostate vaporization for bladder outflow obstruction using a Gyrus PlasmaKinetic Plasma V bar. MATERIALS AND METHODS: A total of 160 men were enrolled in a prospective, randomized trial. Those at higher risk for cancer were excluded by prostate specific antigen and digital rectal examination with or without transrectal ultrasound biopsy. A total of 81 men underwent prostate vaporization and 79 underwent transurethral prostate resection. Preoperative International Prostate Symptom Score and quality of life score, uroflowmetry, post-void residual urine and transrectal ultrasound prostate volume were recorded. Preoperative and postoperative serum hemoglobin, hematocrit and sodium were measured. Perioperative fluid absorption was calculated using weighing on table and blood loss using the Hemocue system. Longer followup of International Prostate Symptom Score and quality of life score, uroflowmetry and post-void residual urine was available in 149 men, including 76 who underwent prostate vaporization and 73 who underwent transurethral prostate resection. Data were analyzed using the 1 or 2-sample t and chi-square tests. RESULTS: The 2 groups were comparable in all preoperative parameters. Perioperative fluid absorption, intraoperative blood loss, preoperative and postoperative serum hematocrit, and sodium changes were not statistically different. Mean resection time was 4 minutes shorter for transurethral prostate resection (28.5 vs 32.6 minutes, p = 0.08). Patients with transurethral prostate resection showed a greater hemoglobin decrease (1.39 vs 0.8 gm/dl, p = 0.002) and required more irrigation postoperatively (28.3 vs 20.4 l, p = 0.001). Four patients with transurethral prostate resection required transfusion compared with none who underwent prostate vaporization. After transurethral prostate resection hospital stay was longer (3.36 vs 3.02 days, p = 0.03). Cancer was detected in 8 patients with transurethral prostate resection (10%), of whom 7 are under prostate specific antigen surveillance and 1 received radical radiotherapy. Mean long-term followup was 258 days (range 82 to 884). Prostate vaporization and transurethral prostate resection were equally effective at followup, as evidenced by changes in maximum urine flow, International Prostate Symptom Score, quality of life score and post-void residual urine. CONCLUSIONS: The 2 operations are highly effective in experienced hands. PlasmaKinetic prostate vaporization resulted in less postoperative bleeding and a slightly shorter hospital stay. The lack of a histological specimen with this version of PlasmaKinetic prostate vaporization may mean that clinically significant cancers are missed.

Adult↗
PubMed1994

Prostate-specific antigen. Current role in diagnostic pathology of prostate cancer.

Prostate-specific antigen is the most important, accurate, and clinically useful biochemical marker in the prostate. It is manufactured by the secretory epithelial cells and drains into the ductal system, where it catalyzes the liquefaction of the seminal coagulum after ejaculation. Serum levels are normally less than 4 ng/mL (monoclonal) but vary according to patient age and race; any process that disrupts the normal architecture of the prostate allows diffusion of prostate-specific antigen into the stroma and microvasculature. Elevated serum prostate-specific antigen levels are seen with prostatitis, infarcts, hyperplasia, and transiently after biopsy, but the most clinically important increases are seen with prostatic adenocarcinoma. Cancer produces less prostate-specific antigen per cell than benign epithelium, but the greater number of malignant cells and the stromal disruption associated with cancer account for the increased serum prostate-specific antigen level. Serum prostate-specific antigen level correlates positively with clinical stage, tumor volume, histologic grade, and the presence of capsular perforation and seminal vesicle invasion; despite these strong correlations, its value is limited in predicting stage for individual patients. It may also predict the presence of lymph node metastases, bone metastases, and survival after androgen-deprivation therapy. The use of prostate-specific antigen has resulted in an increase in the early detection rate of cancer, and it is now advocated for annual routine use in men older than 40 years who are at increased risk and in all men older than 50 years. It is a test with high sensitivity and specificity that is rapid, inexpensive, minimally invasive, and acceptable to patients. In addition to serum prostate-specific antigen level, five derivatives of serum prostate-specific antigen were recently described that may increase the predictive value by accounting for confounding variables such as patient age, prostate volume, and cancer volume: age-specific reference ranges, prostate-specific antigen density, prostate-specific antigen velocity, prostate-specific antigen cancer density, and prostate-specific antigen doubling times. Serum prostate-specific antigen detects a heterogeneous group of cancers (clinical stage T1c) that are clinically important and potentially curable. Immunohistochemical expression of prostate-specific antigen in tissue sections allows determination of the prostatic origin of some metastatic adenocarcinomas, although extraprostatic expression of prostate-specific antigen has been reported in several tissues and tumors, including periurethral gland adenocarcinoma in women, rectal carcinoid, and extramammary Paget disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Forecasting↗
PubMed2000

Increased expression of fibroblast growth factor 6 in human prostatic intraepithelial neoplasia and prostate cancer.

Fibroblast growth factors (FGFs) are known to play an important role in the growth of normal prostatic epithelial cells. In addition to their effects on proliferation, FGFs can promote cell motility, increase tumor angiogenesis, and inhibit apoptosis, all of which play an important role in tumor progression. To determine whether FGFs are overexpressed in human prostate cancers, we analyzed 26 prostate cancer RNAs by reverse transcription-PCR for expression of FGF3, FGF4, and FGF6, which cannot be detected in normal prostate tissue by this technique. Fourteen of 26 prostate cancers expressed FGF6 mRNA. No expression of FGF3 or FGF4 was detected. An ELISA of tissue extracts of normal prostate, high-grade prostatic intraepithelial neoplasia (PIN), and prostate cancer for FGF6 showed that this growth factor was undetectable in normal prostate but was present at elevated levels in 4 of 9 PIN lesions and in 15 of 24 prostate cancers. Immunohistochemical analysis with anti-FGF6 antibody revealed weak staining of prostatic basal cells in normal prostate that was markedly elevated in PIN. In the prostate cancers, the majority of cases revealed expression of FGF6 by the prostate cancer cells themselves. In two cases, expression was present in prostatic stromal cells. Exogenous FGF6 was able to stimulate proliferation of primary prostatic epithelial and stromal cells, immortalized prostatic epithelial cells, and prostate cancer cell lines in tissue culture. FGF receptor 4, which is the most potent FGF receptor for FGF6, is expressed in the human prostate in vivo and in all of the cultured cell lines. Thus, FGF6 is increased in PIN and prostate cancer and can promote the proliferation of the transformed prostatic epithelial cells via paracrine and autocrine mechanisms.

Cell Division↗
PubMed1992

Prostate-specific antigen and diagnosing early malignancies of the prostate.

Prostate-specific antigen is a kallikrein-like serine protease that is produced exclusively by the epithelial cells of all types of prostatic tissue, benign and malignant. Physiologically, it is present in the seminal fluid at high concentration and functions to cleave the high molecular weight protein responsible for the seminal coagulum into smaller polypeptides. This action results in liquefaction of the coagulum. Prostate-specific antigen is also present in the serum and can be measured reliably by several different assays. Although the protein is prostate-specific, it is not prostate-cancer-specific. As a result, benign conditions such as benign prostatic hyperplasia, prostatitis and infarction, as well as prostatic intraepithelial neoplasia, can be associated with elevated serum levels of prostate-specific antigen. Approximately 25% of men with benign prostatic hyperplasia have an elevated serum value of prostate-specific antigen, whereas 35% to 40% of patients with organ-confined prostate cancer have a level within the reference range. Prostate-specific antigen can identify some cancers not detectable by digital rectal examination; alternatively, this examination can identify cancers not detectable from the serum prostate-specific antigen concentration. Thus, the most complete evaluation of the prostate gland is achieved when both the prostate-specific antigen value and the digital rectal examination are used. The density and the rate of change of serum prostate-specific antigen are new concepts to improve the ability of prostate-specific antigen to detect early prostate cancer. Preliminary results are encouraging, but additional studies are required to determine the true usefulness of these new variables. Thus, in 1992, determination of the prostate-specific antigen value is a valuable new tool for the practicing physician and will be instrumental in our campaign to diagnose clinically significant prostate cancer at an early, curable stage.

Amino Acid Sequence↗
PubMed1999

The necessity of a second prostate biopsy cannot be predicted by PSA or PSA derivatives (density or free:total ratio) in men with prior negative prostatic biopsies.

Serum prostate specific antigen, prostate specific antigen density and free:total prostate specific antigen are known to be useful for determining the risk of prostate cancer in patients undergoing prostate cancer screening. The patient with a positive biopsy presents no future prostate specific antigen dilemma. Those with negative biopsies often go on to numerous repeat biopsies. Our goal was to establish criteria that could be used to identify patients who will require repeat prostate biopsies (possibly false negative initial biopsy), while not exposing the low risk population (probable true negative initial biopsy) to additional invasive procedures. Between March 1991 and March 1998, 148 patients who had a biopsy for an elevated prostate specific antigen value (4.1-10.0) or an altered digital rectal examination, had no cancer found in the specimen. From these, 51 (34.4%) had repeated biopsies, while the others persisted on close follow-up. We examined their serum prostate specific antigen, prostate specific antigen density and free:total prostate specific antigen value, as well as their age and histology results of the initial and repeat biopsy, to determine if any predictor of the need for a repeat biopsy could be identified. Eight (15.7%) from 51 men who had repeat biopsy had prostate cancer detected. Forty three (84.3%) patients persisted with a negative biopsy, despite filling the criteria for re-biopsy. Multivariate analysis failed to identify any significant predictors of prostate cancer in the repeat biopsy group. Despite initial success, the prostate specific antigen derivatives and free:total prostate specific antigen have not safely limited the number of biopsies performed for an abnormal prostate specific antigen (4.1-10.0). Neither prostate specific antigen density nor free:total prostate specific antigen predicted the need for repeat biopsy in this specific group. The results of this ongoing study demonstrate that to date, prostate specific antigen and prostate specific antigen derivatives can not be utilized to determine which patients will be at high risk for requiring repeat prostate biopsy. All patients must be closely monitored for evidence of a change in status from benign to malignant disease, and new markers for this purpose are urgently needed.

Aged↗
PubMed1994

Prostatic fluid inflammation in prostatitis.

We studied expressed prostatic secretions from 106 patients with prostatitis to determine the longitudinal course of prostatic fluid inflammation. Prostatic fluid specimens were collected from 14 patients with acute bacterial, 13 with chronic bacterial and 79 with abacterial prostatitis. White blood cells per high power microscopic field of the expressed prostatic secretion were counted under a cover slip. Inflammation in the expressed prostatic secretion was considered to be consistent with prostatitis if there were 10 or more white blood cells per high power field. The 14 patients with acute bacterial prostatitis had a mean of 10 visits with a mean followup of 59 months. Inflammation resolved within 1 month in 9 patients with acute bacterial prostatitis but it recurred in 5 other patients in association with urinary tract infection. The 13 patients with chronic bacterial prostatitis had a mean of 10 visits with a mean followup of 58 months. Episodic inflammation in the expressed prostatic secretion associated with urinary tract infection was seen in all patients during followup. The 79 patients with abacterial prostatitis had a mean of 7 visits with a mean followup of 40 months. Resolution of inflammation in the expressed prostatic secretion occurred in 9 patients (11%). Inflammation in the expressed prostatic secretion at followup was seen in 70 patients (89%), and 27 of the 79 patients (34%) had 10 or more white blood cells per high power field of expressed prostatic secretion in all subsequent specimens. In cases of abacterial prostatitis, neither the initial expressed prostatic secretion white blood count nor the presence of symptoms reliably predicted subsequent inflammation. The data suggest that prostatic inflammation resolves in most patients with acute bacterial prostatitis and is episodic in patients with chronic bacterial or abacterial prostatitis.

Acute Disease↗
PubMed2000

Short term neoadjuvant androgen deprivation therapy does not affect prostate specific membrane antigen expression in prostate tissues.

BACKGROUND: Prostate specific membrane antigen (PSMA) is a transmembrane glycoprotein highly expressed in benign prostate secretory-acinar epithelium and prostate carcinoma. The results of several studies suggest that PSMA expression is increased in prostate carcinoma cell lines subjected to androgen deprivation and in androgen-independent tumors. The authors studied the effects of short term (3-month) androgen deprivation on PSMA expression in prostate carcinoma specimens using two anti-PSMA monoclonal antibodies (mAbs), 7E11 and PM2J004.5. METHODS: The study included patients with clinically localized prostate carcinoma who were prospectively randomized into 1 of 2 treatment groups: 3 months of neoadjuvant androgen deprivation therapy followed by radical prostatectomy (ADT/RP), or radical prostatectomy (RP) alone. Representative formalin fixed, paraffin embedded prostate sections were immunostained with the anti-PSMA mAbs 7E11 and PM2J004.5 by the streptavidin-biotin method. The authors recorded the staining intensity and the percentage of positive cells stained in benign epithelium, high grade prostatic intraepithelial neoplasia (PIN), and prostate carcinoma. They compared the results of 7E11 with those of PM2J004.5 in benign epithelium, high grade prostate, and carcinoma and also compared the results between the two treatment groups (ADT/RP vs. RP alone). RESULTS: Both anti-PSMA mAbs stained benign secretory-acinar epithelium, high grade PIN, and prostate carcinoma. In both treatment groups, PM2J004.5 reacted with a significantly greater percentage of cells (P < 0.001) and with significantly greater intensity (P < 0.001) compared with 7E11 in benign epithelium and prostate carcinoma. With both anti-PSMA mAbs, the percentage of cells stained and the intensity of staining in high grade PIN was similar to that in prostate carcinoma. In the group that received RP alone, the percentage of cells stained and the intensity of staining with 7E11 were significantly greater in high grade PIN and prostate carcinoma compared with benign epithelium (P < 0.001), and the intensity of staining with the PM2J004.5 was significantly greater in high grade PIN and prostate carcinoma compared with benign epithelium (P < 0.001). In the ADT/RP group, the percentage of cells stained and the intensity of staining with 7E11 and PM2J004.5 were significantly greater in prostate carcinoma compared with benign epithelium (P < 0.006). PSMA staining did not correlate with either Gleason score (in the group that received RP alone) or pathologic stage (in both the RP-alone and ADT/RP groups) and did not differ between the two treatment groups. CONCLUSIONS: Short term neoadjuvant ADT does not affect PSMA expression in benign prostate secretory-acinar epithelium, high grade PIN, or prostate carcinoma. Prostate carcinoma and high grade PIN express significantly higher levels of PSMA than benign prostate secretory-acinar epithelium. Compared with 7E11, the PM2J004.5 anti-PSMA mAb is a more sensitive immunohistochemical marker of prostate carcinoma in formalin fixed, paraffin embedded tissue.

Aged↗