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PubMed1998

Two consecutive sets of transrectal ultrasound guided sextant biopsies of the prostate for the detection of prostate cancer.

PURPOSE: We investigated the role of performing 2 consecutive sets of transrectal ultrasound guided sextant biopsies of the prostate in a single office visit as the protocol for detecting prostate cancer in men presenting for the first time with an abnormal digital rectal examination and/or elevated serum prostate specific antigen (PSA). MATERIALS AND METHODS: A total of 137 consecutive men presenting for the first time with a clinically localized prostate nodule on digital rectal examination and/or elevated serum PSA based upon age specific reference ranges underwent 2 consecutive sets of sextant prostate biopsies under transrectal ultrasound guidance in a single office visit. The 2 sets of biopsies were processed and analyzed separately by pathologists. RESULTS: Adenocarcinoma of the prostate was diagnosed in 43 of the patients (31%) undergoing biopsy. Adenocarcinoma of the prostate was diagnosed in only the second set of biopsies in 13 cases (10%). High grade prostatic intraepithelial neoplasia without adenocarcinoma of the prostate was observed in 18 of the first set of biopsies (15%). High grade intraepithelial neoplasia without adenocarcinoma of the prostate was the only pathological diagnosis in the second set of biopsies in 3 cases. The second set of biopsies provided important new clinical information related to prostate cancer in 20 cases (28%) and increased the number of cancers detected by 30%. In addition, 14 patients with high grade intraepithelial neoplasia who would have required a second set of biopsies were found not to have adenocarcinoma of the prostate. Prostate cancer was detected in 43, 27 and 24% of men with prostate volumes less than 30, 30 to 50 and greater than 50 cc, respectively. The percentage of prostate cancers detected only in the second set of biopsies was not significantly related to prostate size. CONCLUSIONS: Two consecutive sets of transrectal ultrasound guided sextant biopsies of the prostate performed in a single office visit represent a cost-effective biopsy strategy for men presenting with an abnormal digital rectal examination and/or elevated serum PSA. The benefits include increasing the detection of adenocarcinoma of the prostate and providing the recommended second set of biopsies for high grade intraepithelial neoplasia without increased morbidity or cost.

Adenocarcinoma↗
PubMed2003

Free prostate-specific antigen improves prostate cancer detection in a high-risk population of men with a normal total PSA and digitalrectal examination.

OBJECTIVES: Uncertainty exists regarding optimal prostate cancer screening parameters for high-risk populations. The purpose of this study is to report the use of percent free prostate-specific antigen (PSA) as an indication for biopsy in men at increased risk for developing prostate cancer who have a normal digital rectal examination (DRE) and total PSA level between 2 and 4 ng/mL. METHODS: African-American men and men with at least one first-degree relative with prostate cancer are eligible for enrollment into the Prostate Cancer Risk Assessment Program (PRAP) at our institution. Between October 1996 and April 2002, 310 asymptomatic high-risk men with no history of prostate cancer, benign prostatic hyperplasia (BPH), or prostatic intraepithelial neoplasia (PIN) were screened in the PRAP with DRE and total PSA. Percent free PSA was obtained in men with a total PSA between 2 and 10 ng/mL. Men with a normal DRE and total PSA between 2 and 4 ng/mL were advised to undergo transrectal ultrasound-guided (TRUS) biopsies of the prostate if the percent free PSA was less than 27%. Other indications for biopsy included an abnormal DRE or a total PSA greater than 4 ng/mL. The primary endpoint evaluated was prostate cancer detection in high-risk men with a benign prostate examination, a normal total PSA between 2 and 4 ng/mL, and percent free PSA less than 27%. RESULTS: Of the 310 men, 174 (56%) were African American and 202 (65%) had at least one first-degree relative with prostate cancer. Sixty-two of the 310 men were referred for prostate biopsy, and 40 of 62 had biopsy performed. Twenty-one of 40 men were diagnosed with prostate cancer for a cancer detection rate of 53% in all men undergoing biopsy and an overall cancer detection rate of 6.8% in this high-risk population. Thirty-seven high-risk men (median age 54 years) with a total PSA level between 2 and 4 ng/mL (median 2.7 ng/mL) and a normal DRE were found to have a percent free PSA level of less than 27% (median 16%, range 8% to 25%). Twenty-three of these 37 men (62%) proceeded with the recommended prostate biopsy. Prostatic adenocarcinoma was diagnosed in 12 of 23 men for a cancer detection rate of 52% in men undergoing biopsy and 32% in all men with a normal DRE, a total PSA between 2 and 4 ng/mL, and a percent free PSA less than 27%. All positive biopsies demonstrated clinically significant Gleason score 6 or 7 disease. In all men electing radical prostatectomy, bilateral organ-confined disease (pT2bN0M0) was confirmed. CONCLUSIONS: In this unique population of men at high risk for prostate cancer, a percent free PSA of less than 27% was found to be useful for detecting early-stage but clinically significant cancers in men with a total PSA value between 2 and 4 ng/mL and normal DRE findings.

Biopsy, Needle↗
PubMed2002

Relationship between prostate volume, prostate-specific antigen nadir, and biochemical control.

PURPOSE: In patients treated with definitive three-dimensional conformal radiotherapy (3D-CRT) for localized prostatic adenocarcinoma, we sought to evaluate the relationship between pretreatment prostate gland volume and posttreatment prostate-specific antigen (PSA) nadir, as well as the relationship of prostate volume and PSA nadir with biochemical control (bNED). Two subgroups were studied: favorable (PSA <10 ng/mL, Gleason score 2-6, and T1-T2A) and unfavorable (one or more: PSA >/=10 ng/mL, Gleason score 7-10, T2B-T3). MATERIALS AND METHODS: A total of 655 men (n = 271 favorable and 384 unfavorable) were treated with 3D-CRT alone between May 1989 and November 1997. All patients had information on prostate volume and a minimum follow-up of 24 months (median 56, range 24-126). Of the 655 men, 481 (n = 230 favorable and 251 unfavorable) remained bNED at time of analysis, with biochemical failure defined in accordance with the American Society for Therapeutic Radiology and Oncology consensus definition. Factors analyzed for predictors of bNED included pretreatment prostate volume, posttreatment PSA nadir, pretreatment PSA, palpation T stage, Gleason score, center of the prostate dose, and perineural invasion (PNI). We also analyzed pretreatment prostate volume and its correlation to prognostic factors. For bNED patients, the relationship between PSA nadir and prostate volume was evaluated. RESULTS: On multivariate analysis, prostate volume (p = 0.04) and palpation T stage (p = 0.02) were the only predictors of biochemical failure in the favorable group. On multivariate analysis of the unfavorable group, pretreatment PSA (p <0.0001), Gleason score (p = 0.02), palpation T stage (p = 0.009), and radiation dose (p <0.0001) correlated with biochemical failure, and prostate volume and PNI did not. For all 481 bNED patients, a positive correlation between pretreatment volume and PSA nadir was demonstrated (p <0.0001). Subgroup analysis of the favorable and unfavorable patients also demonstrated a positive correlation between prostate volume and PSA nadir (p = 0.003 and p = 0.0002, respectively). Using multiple regression analysis, the following were found to be predictive of PSA nadir in all bNED patients: prostate volume (p <0.0001), pretreatment PSA (p <0.0001), palpation T stage (p = 0.0002), and radiation dose (p = 0.0034). Gleason score and PNI were not predictive. For the favorable group, palpation T stage (p = 0.0006), pretreatment PSA (p = 0.0083), prostate volume (p = 0.0186), and Gleason score (p = 0.0592) were predictive of PSA nadir, and PNI and radiation dose were not predictive. In the unfavorable group, prostate volume (p = 0.0024), radiation dose (p = 0.0039), pretreatment PSA (p = 0.0182), and palpation T stage (p = 0.0296) were predictive of PSA nadir, and Gleason score and PNI were not predictive. CONCLUSION: This report is the first demonstration that prostate volume is predictive of PSA nadir for patients who are bNED in both favorable and unfavorable subgroups. PSA nadir did not correlate with bNED status in the favorable patients, but it was strongly predictive in the unfavorable patients. Prostate gland volume was also predictive of bNED failure in the favorable but not the unfavorable group.

Aged↗
PubMed2006

Predictive value of prostatic adenocarcinoma after a negative prostate biopsy.

OBJECTIVE: To investigate the predictive value (PV) for all prostate cancers and for clinically significant cancer undiagnosed after a 10-core biopsy protocol, as the 10-core transrectal ultrasonography-guided biopsy is considered the standard technique of prostatic biopsy due to its high rate of detection of prostatic adenocarcinoma. PATIENTS AND METHODS: In all, 132 consecutive radical prostatectomy (RP) specimens, with their corresponding 10-core biopsies, were reviewed. Cases with unilateral core involvement by prostate cancer were retained for study. Morphometric analysis was conducted on the biopsy-negative hemi-prostates to determine the PV of the biopsy protocol with respect to the size, position and clinical significance of the lesion. RESULTS: In all, 70 resected prostates (RP) had unilateral core involvement by prostate cancer. In 38 cases, there was cancer in the biopsy-negative hemi-prostates (group 1); in the remaining 32 the hemi-prostates were free of cancer (group 2). Group 1 was categorized by morphometric criteria. Specifically, 23 cases had one to eight foci of prostate cancer in the posterior nontransitional zone (NTZ) (group 1a), while 15 had two to six foci of prostate cancer in the transitional zone (TZ), or the anterior horn (AH) of the peripheral zone or the TZ and AH (group 1b). There were two cases with clinically significant prostate cancer in group 1a, and six in group 1b. CONCLUSIONS: The PV of a negative five-core biopsy protocol on a hemi-prostate is 54% for prostate cancer and 11% for clinically significant prostate cancer. Most clinically significant prostate cancers were in the AH/TZ of the prostate.

Adenocarcinoma↗
PubMed2000

Serum levels of insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-3, and prostate-specific antigen as predictors of clinical prostate cancer.

Insulin-like growth factors (IGFs) may play a role in prostate growth, hyperplasia, and malignancy. High plasma IGF-I has been associated with increased prostate cancer risk. In a prospective, cohort, case-control study in the Baltimore Longitudinal Study on Aging population, we examined prostate volume by magnetic resonance imaging, and prostate-specific antigen (PSA), IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) in sera obtained approximately 9 yr before diagnosis of prostate cancer in cases (n = 72) or age-matched controls (n = 127) and in 76 additional Baltimore Longitudinal Study on Aging men (normal subjects) with measured prostate volumes and no prostate cancer. We calculated adjusted odds ratios (OR) by logistic regression, relative risks for significant ORs, and receiver operator curves for prostate cancer, using serum measures alone and in combination. Adjusted ORs for the high vs. low tertile were: for IGF-I, 3.1 [confidence interval (CI), 1.1-8.7]; for IGF-II, 0.2 (CI, 0.07-0.6); for IGFBP-3, 0.71 (CI, 0.3-1.7); and for PSA, 12.5 (CI, 3.8-40.9). For significant ORs, relative risk estimates remained significant at 2.0 for IGF-I, 0.3 for IGF-II, and 5.5 for PSA. Receiver operator curves showed PSA to be the most powerful predictor of prostate cancer. Adding IGF-II to PSA improved prediction. IGF-II was significantly and inversely related (r = -0.219; P < 0.01) and PSA was directly and significantly related (r = 0.461; P < 0.0001) to prostate volume, whereas IGF-I and IBFBP-3 were not. High IGF-I and low IGF-II are independently associated with increased risk of prostate cancer, but PSA level is a much stronger predictor of prostate cancer in the ensuing 10 yr than either IGF-I or IGF-II. The absence of a relationship of IGF-I to prostate size is inconsistent with increased ascertainment in men with large prostates as the source of greater prostate cancer risk associated with IGF-I. Our data suggest that IGF-II may inhibit both prostate growth and development of prostate cancer.

Baltimore↗
PubMed2006

[Penetrability and therapeutic effect of vancomycin to the prostates of rats with bacterial prostatitis (BP) or BPH-BP].

OBJECTIVE: To explore the penetrability and therapeutic effect of vancomycin to the prostates of rats with bacterial prostatitis (BP) or benign prostate hyperplasia (BPH)-BP. METHODS: The experimental rats with BP or BPH-BP were injected with vancomycin through the tail vein. The prostate tissues and sera were isolated respectively from the rats at 10 min to approximately 24 h after treatment and the antibiotic activities of the samples were detected by serial dilution test and agar diffusion test. The rats with BP or BPH-BP were treated with vancomycin by intravenous injection daily for 5 days. The prostates were collected the second day after injection and bacteria were isolated and determined. One to five weeks after treatment, the prostates of the animals were isolated and pathologic tests were done. RESULTS: No bacteria could be isolated from the prostates of the normal rats, but positive isolation was achieved from the prostates of the infected animals 28th day after infection. In the first 4 days after treatment, a decrease of bacteria could be detected in the prostate samples of the rats treated with BP or BPH-BP. After 5th day, no bacteria could be detected from 91.7% prostates of the treated groups. Obvious antibiotic activity in both sera and prostates could be detected 10 to approximately 150 min after the antibiotic injection. Antibiotic activity of the prostate tissues could be lower or higher than or equal to that of the sera in the same period. Pathologic tests detected obvious exudation and leukocyte invasion in the prostate tissues of the BP rats and gland proliferation in the BPH rats. Vancomycin treatment and the consequent reduction of bacteria obviously alleviated the inflammatory pathological changes in the prostates of the BP rats. CONCLUSION: Vancomycin given intravenously has more penetrability to the prostates of either BP or BPH-BP rats. The antibiotic concentration in the prostate tissues may be equal to or higher than that of the sera, so that the susceptive bacteria in the prostates will be killed and the alleviation of the inflammation and repair of the tissues accelerated effectively.

Animals↗
PubMed1983

[The significance of prostatic serum acid phosphatase as a tumor marker in prostatic cancer].

The levels of prostatic serum acid phosphatase (PSAP) were determined by radioimmunoassay using RIA-Quant PAP test kit on 14 normal females, 56 normal males, 25 patients with prostatitis, 74 patients with benign prostate hypertrophy, 129 patients with prostatic cancer, 50 patients with nonprostatic malignancies, and 16 post radical cystectomized males, making 364 cases in all. To diagnose prostatic cancer, a PSAP level of over 3.0 ng/ml was determined positive for differential diagnosis of prostatitis, benign prostate hypertrophy, and prostatic cancer. According to this criterium, the positive rate for each type of disease was: 0% for prostatitis, 5.4% for benign prostate hypertrophy, 80.6% for untreated prostatic cancer, and 2% for nonprostatic malignancies. In benign prostate hypertrophy, the cases with urethral catheters showed a tendency of high PSAP level, but no significant difference was observed. PSAP positive rates of untreated prostatic cancer by stage are 0% for Stage A, 57.1% for Stage B, 85.7% for Stage C, 100% for Stage D1, and 94.1% for Stage D2 cases at a high stage showing high positive rates. However, there seems to be a limit for the diagnosis of early prostatic cancer. As for the relationship between the grade of untreated prostatic cancer and PSAP, well differentiated tumors showed higher levels of PSAP in the study with cases of the same stage. However, with all the cases, less well differentiated tumors showed higher levels of PSAP. As a tumor marker for prostatic cancer in the observation of treatment response, the PSAP level of over 2.0 ng/ml was determined positive. The relationship between the judgement of treatment response and PSAP was: Objective stable for its increase or decrease within the normal range; progressive disease for its elevation from normal to positive level, or increase or decrease of PSAP level within the positive range; Objective partial regression or objective stable for normalization from positive level. The PSAP level in the internal iliac vein of the patients with prostatic cancer tended to be higher than that in the femoral vein or antecubital vein.

Acid Phosphatase↗
PubMed2003

Glycoprotein A-80 in the human prostate: immunolocalization in prostatic intraepithelial neoplasia, carcinoma, radiation failure, and after neoadjuvant hormonal therapy.

OBJECTIVES: To review the expression of A-80 in prostate cancer and prostatic intraepithelial neoplasia and compare it with that of normal and hyperplastic prostatic tissue. The ability to recognize cancer after androgen deprivation therapy and residual and/or recurrent cancer after radiotherapy using A-80 staining was also examined. A-80 is a glycoprotein linked to exocrine differentiation that shows little or no expression in normal exocrine cells, but is selectively overexpressed in dysplasias and adenocarcinomas. METHODS: We studied 277 prostate samples with a monoclonal antibody (MAb) to A-80. We applied this MAb to paraffin sections of specimens of fetal (n = 12), benign prostatic hyperplasia (n = 26, from transurethral prostate resection specimens), atypical adenomatous hyperplasia (n = 11), prostate cancer (n = 103, from radical prostatectomy specimens), and autopsy (n = 7) tissue. In addition, 54 prostatectomy specimens after androgen-deprivation therapy and 64 specimens after radiotherapy were similarly studied. RESULTS: MAb A-80 stained the epithelial component of all 12 prostate specimens from fetal tissue; no staining was seen in normal adult prostatic tissue (0 of 7). In benign prostatic hyperplasia, sporadic cells reacted in 13% of cases (4 of 30); the atypical adenomatous hyperplasia samples were all negative (0 of 11). In patients with prostate cancer, more than 99% (102 of 103) stained positive, regardless of the grade or stage of cancer. Low and high-grade prostatic intraepithelial neoplasia reacted in 73% (38 of 52) and 92% (77 of 84) of cases, respectively. All 64 (100%) salvage prostatectomy samples after external beam radiotherapy stained positive for A-80. Carcinoma subsequent to neoadjuvant hormonal therapy stained positive in 98% (53 of 54) of cases. CONCLUSIONS: A-80 is useful in differentiating benign prostatic hyperplasia and atypical adenomatous hyperplasia from prostate cancer. Also, the strong A-80 reactions in most high-grade prostatic intraepithelial neoplasia provide strong molecular support to the precancerous nature of the lesion. In particular, A-80 staining of biopsies may be useful in detecting residual and/or recurrent prostate carcinoma after radiation or hormonal therapy.

Adenocarcinoma↗
PubMed1998

High grade prostatic intraepithelial neoplasia in military working dogs with and without prostate cancer.

BACKGROUND: High grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer and is commonly found in men undergoing prostatic needle biopsy for suspected cancer. Recent work has demonstrated that pet dogs, like humans, develop PIN spontaneously and in association with prostate cancer. Pet dogs are the most domesticated animal, sharing the habitat and oftentimes the diet of their owners. If PIN and prostate cancer are strongly related to environmental factors, then the prevalence of these findings might differ in a population of dogs such as military working dogs which is not exposed to the habitat and diet of humans. In this study, we determined the prevalence of PIN in prostates of aged military working dogs with and without prostatic adenocarcinoma. METHODS: Cases were selected from the military working dog slide and tissue archive at the Armed Forces Institute of Pathology, Washington, DC. The most recent 329 necropsies (1991 to 1996) were examined histologically by multiple reviewers; of these, 199 dogs (60%) were found to have evaluable prostatic tissue. In addition, the most recent 50 necropsies (1958 to 1996) with the diagnosis of prostatic cancer were examined, of which 25 cases (50%) were found to have evaluable prostatic adenocarcinoma. In most cases, a single large transverse section of prostatic tissue was available for review. Medical records for each dog were reviewed independently, and age, clinical history, indications for euthanasia, and other health problems were recorded. RESULTS: High grade PIN was identified in 3% of dogs (6 of 199 dogs) without prostate cancer. A total of 50.8% of dogs in this study group (101 of 199 dogs) were known to be sexually intact, 26.7% of dogs (53 of 199 dogs) were castrated, and the status of the remaining 22.6% of dogs (45 of 199 dogs) was unknown. High grade PIN was present in 18 of 25 dogs (72%) with prostatic adenocarcinoma. Of these cases, 11 dogs (44%) were castrated, 4 dogs (16%) were intact, and the status of 10 dogs (40%) dogs was unknown. Gleason scores ranged from 6 to 10, with a mean of 8.4 and a median of 8. CONCLUSIONS: High grade PIN is present in a small but substantial number (3%) of military working dogs. Of military working dogs with prostatic adenocarcinoma, 72% had high grade PIN. The true prevalence in each of these cohorts is likely to be higher given the sampling variation inherent in evaluating a single random histologic section. Aged male dogs seem to have substantial clinical utility as an animal model for prostatic carcinogenesis. We recommend that serial sectioning and total embedding of the prostate should be used to more thoroughly characterize premalignant and malignant diseases in aged military working dogs. This method will provide important data to determine whether a model of spontaneous PIN in elderly dogs may have clinical utility in developing strategies directed toward preventing and treating prostate.

Adenocarcinoma↗
PubMed1996

Antibody immunoglobulin G (IgG) against human prostatic specific antigen (PSA) as a carrier protein for chemotherapeutic drugs to human prostate tumors: Part 1. A double immunofluorescence analysis.

BACKGROUND: Adenocarcinoma of the prostate (CaP) is the the second highest cause of cancer deaths in U.S. males. Current chemotherapeutic and/or endocrine treatments do not specifically and selectively target tumor cells of prostate cancer and benign prostatic hyperplasia (BPH). We hypothesized that because of the specific binding characteristics of antibody immunoglobulin G (IgG) to human prostatic-specific antigen (PSA), PSA-IgG could function as a carrier protein for conjugated chemotherapeutic drugs and that the immunoconjugate would selectively bind to prostatic epithelial cells and their tumors, but not to epithelial cells of unrelated organs. Our objective was to test the hypothesis using human prostatectomy specimens. METHODS: WE used several derivatives of 5'-fluorouracil, namely, 5'-fluoro- 2'-deoxyuridine (5'-Fu-2'-d), 5'-fluoro-2'-deoxyuridine-5' monophosphate (5'-Fu-2'-d-5'-mp), 5'-fluoro-2'-deoxyuridine-5'-(p-aminophenyl) monophosphate (5'-Fu-2'-d'-5'-amp), to conjugate with rabbit anti-PSA-IgG together with fluorescent markers (such as rhodamine and fluorescein or fluorescein isothiocyanate: FITC). Prostate specimens were obtained from prostatectomy patients who had not been treated with cytotoxic drugs before surgery. We evaluated formalin-fixed and paraffin-embedded sections as well as cryostat sections of frozen specimens for localization of PSA-IgG alone and PSA-IgG-drug immunoconjugate using immunoperoxidase (IP) and single and/or double immunofluorescence (IF) localization techniques. RESULTS: Our study showed that the immunoconjugate (PSA-IgG-5'-Fu-2'-d) bound to PSA (molecular size of approximately 34 KDa) on nitrocellulose sheets in Western immunoblots of extracts of BPH and CaP tissues. This binding of immunoconjugate to PSA on immunoblots was similar to that of the unconjugated PSA-IgG. Immunostaining patterns for rabbit anti-PSA-IgG and PSA-IgG-5'-Fu-2'-d immunoconjugate were similar and specific for prostate epithelial cells and their tumors, as revealed by IP techniques. To demonstrate that both the antibody and drug localized in the same group of prostatic epithelial cells, we used an immunoconjugate in which the PSA-IgG was labeled with rhodamine and 5'-Fu-2'-d-5'-amp with FITC. Our study showed that fluorescence for rhodamine and FITC was present in the same group of prostatic epithelial cells. Phase contrast microscopy demonstrated details of prostatic glandular epithelium and connective tissues. Our study showed that fluorescence for rhodamine and FITC and immunostaining by IP techniques were not observed in prostate sections incubated with normal rabbit serum. CONCLUSIONS: We have shown that conjugation of 5'-Fu derivatives to PSA-IgG did not affect either the selectivity or specificity of the antibody for prostatic epithelial cells. Differential immunofluorescence study has shown that PSA-IgG may function as a carrier protein for chemotherapeutic drugs to prostate epithelial cells and their tumors. Furthermore, FITC-labeled 5'-Fu-2'-d did not specifically localize in prostatic glands, kidney, lungs, bladder, or colon. Because of the specificity and selectivity of the immunoconjugate for prostatic epithelial cells and their tumors, the immunoconjugate could be used in small dosages to treat prostatic tumors and such treatment would greatly reduce many unpleasant side effects in patients. This is the first report to show that PSA-IgG can function as an organ specific carrier protein for chemotherapeutic drugs to human prostate epithelium and its tumors.

Antibodies↗
PubMed1982

Decrease in creatine kinase in human prostatic carcinoma compared to benign prostatic hyperplasia.

Many previous studies have shown that a proportion of patients with carcinoma of the prostate have increased activity of the creatine kinase (E.C. 2.7.3.2) isoenzyme designated BB in sera from their peripheral blood. We have analyzed tissues from prostatic hyperplasia of 22 patients and from prostatic carcinoma of 23 additional patients. Prostatic carcinomas contain less (p less than 0.001) creatine kinase activity (units/g) than do prostates with benign prostatic hyperplasia. The facts that (a) histochemical studies that we performed confirmed the observation reported previously by others that creatine kinase activity is found primarily in the epithelial elements of hyperplastic prostates and prostatic carcinomas, (b) the carcinomas that we examined had, on the average, a somewhat larger epithelial component than the hyperplastic prostates that we examined, and (c) prostate cancer was found to contain less creatine kinase activity than hyperplastic prostates suggest that the epithelial cells in prostate cancers contain less creatine kinase activity per cell than do those from hyperplastic prostates. The BB form of creatine kinase accounts for 98% of the activity in prostatic carcinoma and in prostates without cancer. Creatine kinase has been discussed as a possible marker for prostatic carcinoma, and we had hoped that it might be useful for the assay of tumor burden. Our data suggest that, if creatine kinase is to be useful in the monitoring of tumor burden, it will be useful only in the contexts of particular patients studied longitudinally since the creatine kinase activity varies enormously among different prostatic carcinomas.

Aged↗
PubMedDate not supplied

Immunocytochemical localization of an immunoconjugate (antibody IgG against prostatic acid phosphatase conjugated to 5-fluoro-2'-deoxyuridine) in human prostate tumors.

Current chemotherapeutic and/or endocrine treatments for adenocarcinoma of the prostate (CaP) do not selectively target neoplastic prostate cells. Therefore, new approaches are needed to improve treatment for prostate tumors. We hypothesized that because of the specific binding of antibody immunoglobulin G (IgG) against human prostatic acid phosphatase (PAcP), PAcP-IgG could function as a carrier protein for the conjugated chemotherapeutic drugs and that the immunoconjugate would then selectively localize (bind) to epithelial cells of human prostate tumors, but not to epithelial cells of other solid organs. Our objective was to test this hypothesis using human prostate, colon, and kidney tissue samples and human prostate pieces incubated in short-term organ culture. We used derivatives of 5-fluorouracil labeled with fluorescein isothiocyanate (FITC) and rabbit anti-PAcP-IgG tagged with CY3/rhodamine alone or as an immunoconjugate. Localization of PAcP-IgG alone and the immunoconjugate in prostate produced similar and specific immunostaining in prostate epithelial cells and their tumors, but not in epithelia of colon and kidney tissue sections or in prostate sections-treated with normal rabbit serum. Confocal microscopy showed co-localization of CY3 and FITC of the immunoconjugate in the same group of prostate epithelial cells and their tumors. Organ culture studies showed that human prostate tissue samples incubated with normal rabbit serum did not show any fluorescence whereas those cultured with PAcP-IgG immunoconjugate showed fluorescence in glandular epithelial cells. The later study also showed that in organ culture the immunoconjugate had penetrated and labeled prostate glands internal to the cut surfaces. Drug labeled with FITC did not localize specifically in the prostatic epithelium. Analysis of our data has shown that PAcP-IgG was needed for specific localization of the immunoconjugate in prostate glands. We conclude that PAcP-IgG was essential for delivery and binding of the drug in human prostate. This is the first report to show that PAcP-IgG-5-Fu-2'-d-based immunoconjugate was selective and specific to epithelial cells of human prostate and its tumors, as revealed by organ culture, immunocytochemical, and confocal microscopic techniques.

Acid Phosphatase↗
PubMed1997

Prostatic intraepithelial neoplasia in dogs with spontaneous prostate cancer.

Prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer. The prevalence and immunophenotype of PIN in dogs with spontaneous prostate cancer has not been previously described. To investigate the association between PIN and prostate cancer, we evaluated the prostates of dogs with spontaneous prostate carcinoma. The prevalence of PIN was determined in formalin-fixed prostates from 29 dogs with spontaneous prostate cancer. Using immunoperoxidase techniques, we compared basal cell layer integrity (high molecular weight keratin 34 beta-E12), proliferative index (MIB-1), and microvessel density (Factor VIII-related antigen) in 14 prostates which contained benign epithelium, PIN, and carcinoma. PIN was present in 19 of 29 (66%) prostates from dogs with spontaneous prostate cancer. The basal cell layer was intact in benign epithelium, disrupted in 72% of acini with PIN, and absent in carcinoma. The mean proliferative index was 17%, 25%, and 40% for benign epithelium, PIN, and carcinoma, respectively, and these differences were significant. The mean microvessel density in foci of PIN and carcinoma (32 and 39 vessels per mm2, respectively) was greater than in benign epithelium (23 vessels per mm2). High-grade PIN is common in the prostates of dogs with spontaneous carcinoma. The basal cell layer is partially disrupted in PIN, whereas it is absent in prostate cancer. The proliferative index and microvessel density of PIN are intermediate between benign epithelium and cancer. These results are similar to those reported for human PIN and prostate cancer, and indicate that PIN is part of a morphologic continuum in the progression of prostate cancer. To our knowledge, this is the first description of high-grade PIN spontaneously occurring in animals. The canine prostate may serve as a useful model for examining factors that modulate PIN and prostate cancer progression.

Animals↗
PubMed2006

Dutasteride improves objective and subjective disease measures in men with benign prostatic hyperplasia and modest or severe prostate enlargement.

PURPOSE: We determined whether the effect of dutasteride for benign prostatic hyperplasia is influenced by baseline prostate volume using data from 3 phase III clinical trials. MATERIALS AND METHODS: Patients randomized to dutasteride or placebo in the double-blind portion of the phase III studies were eligible to receive 0.5 mg dutasteride daily in a 2-year open label extension in dutasteride/dutasteride and placebo/dutasteride groups. Patients were prospectively stratified according to baseline prostate volume 30 to less than 40 and 40 cc or greater. RESULTS: In patients treated with dutasteride throughout the study (dutasteride/dutasteride group) the mean reduction in prostate volume from baseline to month 48 was 30.3% in those with a baseline prostate volume of 30 to less than 40 cc and 26.2% in those with a prostate volume of 40 cc or greater. Mean improvements in peak urinary flow from baseline to month 48 were 2.7 ml per second regardless of baseline prostate volume. Improvements in the American Urological Association symptom index score were 6.3 in men with a prostate volume of 30 to less than 40 cc and 6.5 in those with a prostate volume of 40 cc or greater. No significant relationships between treatment effect and baseline prostate volume were observed for these parameters. In dutasteride/dutasteride treated patients the risk of acute urinary retention was decreased by 60% in those with a prostate volume of 30 to less than 40 cc and 55% in those with a prostate volume of 40 cc or greater vs values in placebo/dutasteride treated patients (p = 0.036 and <0.001, respectively). The corresponding values for benign prostatic hyperplasia related surgery were 27% and 48% (p = 0.35 and <0.001, respectively). CONCLUSIONS: This analysis demonstrates that dutasteride significantly improves objective (prostate volume and peak urinary flow) and subjective (symptom scores) measures even in patients with only a slightly enlarged prostate (30 to less than 40 cc). The risks of acute urinary retention and benign prostatic hyperplasia related surgery were decreased regardless of baseline prostate volume.

Aged↗
PubMed2000

Concentration of ofloxacin in canine prostate tissue and prostate fluid after intraprostatic injection of biodegradable sustained-releasing microspheres containing ofloxacin.

PURPOSE: Excellent treatment results in chronic prostatitis by direct intra-prostatic injection of antibiotic were reported several decades ago with only minimal scientific background. We examined the distribution, in prostatic tissue and fluid, of the antibiotic in canines after intra-prostatic injection of biodegradable sustained-releasing microspheres containing 12 mg. of ofloxacin. MATERIALS AND METHODS: A total of 36 male dogs, 12 controls and 24 experimental, older than 2 years, were used. Experimental dogs were given biodegradable sustained releasing microspheres containing ofloxacin 12 mg. and poly(D,L-lactic) acid 28 mg., designed to release over more than a 4 week period. The 12 control animals were divided into 2 groups, and oral ofloxacin 100 mg. was given twice a day for 2 and 4 weeks. The 24 experimental animals were divided into 4 subgroups of 6 dogs each, 4 for prostatic tissue and 2 for prostatic fluid level of ofloxacin determination. Anesthesia was initiated with ketamine HCl and xylazine, and maintained with intermittent ketamine HCl. In the experimental groups, 1 ml. of resolved formula was injected into one lobe of surgically exposed prostates. The concentration of ofloxacin was measured by high performance liquid chromatography (HPLC) of blood, prostatic tissue and prostatic fluid. Pilocarpine 0.5 mg./kg. was used for the collection of the prostatic fluid. RESULTS: The total ofloxacin of controls were 2,800 (2 weeks) and 5,600 (4 weeks) mg. In control groups, tissue concentrations of ofloxacin were relatively even at all segments of prostate, 7.4 +/- 0.8 (2 weeks) and 9.2 +/- 1.1 microg./ml. (4 weeks). The blood level ranged between 3.6 to 5.1 microg./ml. The prostatic fluid level ranged from 3.1 to 5.7 microg. /ml. In the experimental groups, the tissue levels of ofloxacin were 10.5 +/- 3.0 (1 week), 13.8 +/- 4.5 (2 weeks), 7.1 +/- 0.9 (3 weeks) and 7.7 +/- 3.0 microg./ml. (4 weeks) in the injected lobe. The opposite lobes were 8.0 +/- 1.1 (1 week), 10.2 +/- 4.2 (2 weeks), 5. 1 +/- 1.4 (3 weeks) and 7.6 +/- 0.8 (4 weeks) microg./ml. The blood level in the experimental groups ranged between 0.16 to 0.59 microg./ml. The prostate fluid level ranged from 2.9 to 6.1 microg./ml. in 8 dogs. Upon pathologic examination, the microspheres were interposed between prostate stroma and their size was reduced over time. CONCLUSIONS: Our study indicates that there is communication between the right and left prostate lobes. Direct injection of biodegradable sustained releasing ofloxacin formula into the prostate may be a substitute for long term antibiotic medication in humans for chronic prostatitis in the future without hurting the minimal inhibitory concentration(MIC)90.

Animals↗
PubMed2001

Prevalence of prostatitis-like symptoms in a population based study using the National Institutes of Health chronic prostatitis symptom index.

PURPOSE: The National Institutes of Health (NIH) chronic prostatitis symptom index was used to determine the prevalence of prostatitis-like symptoms among men (age 20 to 74 years) at risk in a community based study. MATERIALS AND METHODS: The study was a cross-sectional postal survey of men age 20 to 74 years in Lennox and Addington counties, which included a large rural area, 1 major town and a suburban area with a stable population of men representative of Canadian demographics. The questionnaire collected information on 2 domains of chronic prostatitis identified in the NIH chronic prostatitis symptom index, including pain (location, severity and frequency), voiding function (irritative, obstructive), demographics, quality of life, general health and health seeking behavior. The self-reported pain score was used to identify prostatitis-like symptoms in the most discriminating domain. Based on analysis of the index final validation study comparing patients with prostatitis to normal controls and those with benign prostatic hyperplasia, the 2 questions most specific for prostatitis, including perineal and/or ejaculatory pain/discomfort, and a total pain score (0 to 21) 4 or greater were used to identify men with significant prostatitis-like symptoms. RESULTS: A total of 2,987 eligible men received the survey, and it was completed by 868 (29%). Of the men 84 (9.7%) were identified as having chronic prostatitis-like symptoms (mean NIH chronic prostatitis symptom index pain score 9.1 +/- 0.3). The average age of the prostatitis population was 50 years compared with 52 years for men without prostatitis-like symptoms. Prevalence was 11.5% in men younger than 50 years and 8.5% in men 50 years or older. Of the sampled population 57 (6.6%) men had prostatitis-like symptoms and an index pain score 8 or greater (moderate to severe). The index voiding score (0 to 10) was 4.1 +/- 0.5 in men younger than 50 years compared with 1.5 +/- 0.1 for normal controls, and 4.7 +/- 0.4 in those 50 years or older compared with 1.9 +/- 0.1 for normal controls. Of the prostatitis group 60% sought medical help for their symptoms. CONCLUSIONS: In our opinion this community based study using the new prostatitis symptom index confirms that chronic prostatitis-like symptoms are common.

Adult↗
PubMed1997

Systematic 5 region prostate biopsy is superior to sextant method for diagnosing carcinoma of the prostate.

PURPOSE: The number of patients undergoing prostate biopsy has dramatically increased due to prostate specific antigen screening. The low specificity of this screening tool requires prostate biopsy for diagnosis of prostate cancer. The sextant biopsy technique has been used widely with success in diagnosing carcinoma of the prostate. However, concern has arisen that the original sextant method may not include an adequate sampling of the prostate. For many years we have used a method of prostate biopsy that, in addition to sextant biopsies, takes additional biopsies in a systematic fashion, which we call the 5 region prostate biopsy. We conducted a prospective study to determine if our 5 region prostate biopsy technique significantly increases the chances of finding carcinoma of the prostate compared to the sextant biopsy technique. MATERIALS AND METHODS: A total of 119 patients underwent transrectal ultrasound guided needle biopsy of the prostate. In addition to sextant biopsies, cores were taken from the far lateral and mid regions of the gland. Pathological findings of the additional regions were compared to those of the sextant regions. RESULTS: Of the 48 patients with prostate cancer 17 (35%) had carcinomas only in the additional regions, which would have remained undetected had the sextant biopsy technique been used alone (p < 0.05). Of these additional cancers 83% had Gleason scores of 6 or more. CONCLUSIONS: We introduce the 5 region technique of prostate biopsy as a means of significantly increasing the diagnostic yield of prostate biopsy in finding carcinoma of the prostate. We have found this technique to be safe, efficacious and superior to the sextant method of biopsy in identifying prostate cancer at an early but significant stage. The greatest use of the 5 region biopsy technique is in patients who have prostate specific antigen levels between 4 and 10 ng./ml.

Aged↗
PubMed1999

In situ hybridization study of PSP94 (prostatic secretory protein of 94 amino acids) expression in human prostates.

BACKGROUND: The prostatic secretory protein of 94 amino acids (PSP94), also named beta-microseminoprotein, is one of the major proteins secreted by the human prostate. However, its value as a prognostic marker for prostate cancers is still under debate. The aim of the present study was to examine the expression pattern of this protein in fetal, pubertal, and aged human prostates. METHODS: Nonisotopic in situ hybridization using a digoxigenin-labeled riboprobe for PSP94 and immunohistochemistry were used to demonstrate the expression of PSP94 in different regions or zones of fetal, pubertal, and adult human prostates. Its localization pattern was also compared with those of two other major secretory proteins, prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), by immunohistochemistry. RESULTS: PSP94 mRNA and its protein were localized to the secretory epithelium of normal pubertal and adult human prostates. No hybridization signal and immunoreactivity of PSP94 were seen in fetal prostates at 6-7 months of gestation, whereas some glandular cells were positive to PSA and PAP immunostainings. In the adult prostates, PSP94 expression was intense in the acini in the peripheral zone, less intense in the transition zone, and variable in the central zone. Such a zonal expression pattern was more apparent in the pubertal prostates. However, no obvious differential expression pattern was observed in the immunohistochemistry of PAP and PSA, which showed a uniform staining of the secretory epithelia of the acini in all anatomic zones. The hybridization signals and immunoreactivity of PSP94 became reduced or lost in premalignant prostatic intraepithelial neoplastic lesions and different grades of prostatic carcinomas. CONCLUSIONS: Fetal prostates at 6-7 months of gestation already synthesize PSA and PAP but not PSP94. The delayed expression of PSP94 appears to correlate with the development of the prostate gland. A differential expression pattern of PSP94 is demonstrated in different anatomical zones, showing that this protein is more expressed and synthesized in the acini in the peripheral zone than in the central and transition zones. However, such a zonal pattern is not seen in the immunohistochemistry of PSA and PAP. The present study also shows that PSP94 is downregulated in different grades of prostate cancers.

Adolescent↗