Biomedical subjects

David G Bostwick

Publications and source records attributed to David G Bostwick.

At least 37 records · Page 2Linked to original sources

PubMed2004

Amphiregulin expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 93 cases.

BACKGROUND: Amphiregulin (AMP) is a heparin-binding glycoprotein that is structurally and functionally related to epidermal growth factor. Its effects are mediated by the tyrosine kinase activity of the epidermal growth factor receptor (EGF-R), and specific nuclear targeting sequences. AMP induces cell proliferation after androgen stimulation of human prostate cancer cell lines. An autocrine proliferative loop involving AMP, androgen, and EGF-R may, therefore, play a role in prostatic carcinogenesis. The purpose of this study was to compare the expression of AMP in benign prostatic epithelium, high-grade prostatic intraepithelial neoplasia (PIN), and adenocarcinoma. METHODS: We performed an immunohistochemical study of select sections from 93 radical prostatectomies performed at the Mayo Clinic between 1987 and 1991. All patients were previously untreated and found to have pathologic stage T2N0M0 adenocarcinoma after routine handling of surgical specimens. Affinity-purified polyclonal antibody directed against AMP was applied to tissue sections using the streptavidin-biotin method. For each case, the percentage of immunoreactive cells in benign epithelium, PIN, and adenocarcinoma was estimated in 10% increments. Intensity on a scale from 0 (negative) to 3 (strongly immunoreactive) and pattern of expression (nuclear versus cytoplasmic) also were recorded. RESULTS: AMP immunoreactivity was present in benign prostatic epithelium, PIN, and prostatic adenocarcinoma in all cases. The mean percentage of AMP-immunoreactive cells was 53.8% in benign epithelium, 65.9% in PIN, and 74.3% in cancer. Intensity was moderate in all cases. The pattern of expression was usually nuclear in benign epithelium (secretory and basal cells), and usually cytoplasmic or nuclear and cytoplasmic in PIN and adenocarcinoma. There were rare scattered immunoreactive cells in the stroma, ejaculatory duct epithelium, and urethral urothelium. Endothelial cells were invariably unstained. CONCLUSIONS: AMP expression in prostate increases progressively from benign epithelium to PIN and cancer. Increased expression of AMP may contribute to the development of prostatic adenocarcinoma. Predominantly nuclear staining was observed in benign epithelium, whereas cytoplasmic or nuclear and cytoplasmic staining was observed in PIN and adenocarcinoma. The differences in nuclear and cytoplasmic localization of immunoreactivity may reflect the presence of two pathways of activation, and hence varying biological functions of AMP.

Adenocarcinoma↗

PubMed2004

Prostate cancer in native Japanese and Japanese-American men: effects of dietary differences on prostatic tissue.

OBJECTIVES: To investigate the relationship between diet and prostate cancer (CaP) among native Japanese (NJ) and second-generation or third-generation Japanese-American (J-A) men--focusing on the effects of animal fat and soy on prostatic tissues. METHODS: The subjects were 50 Japanese men undergoing radical prostatectomy, 25 NJ living in Nagoya, Japan and 25 U.S.-born J-A men, living in Los Angeles, California. A priori, the NJ men were believed to be a low-fat, high-soy group and the J-A men, a high-fat, low-soy group. The studies included postoperative measurements of diet (Block questionnaire), body fat (bioimpedance), blood, urine, and prostatic biomarkers in malignant and adjacent normal tissue, using a tissue microarray made from the original paraffin blocks. RESULTS: The NJ and J-A men were similar in age (65 to 70 years old; P <0.05), prostate-specific antigen level (7.1 to 8.6 ng/mL), prostate volume (35 to 38 cm3), and Gleason score (5.6 to 6.6), but their body composition differed. J-A men had more body fat (24% versus 19%), higher serum triglyceride levels (245 versus 106 mg/dL), lower estradiol levels (27 versus 31 ng/mL), and much lower urinary soy-metabolite levels (1:3) than NJ men (P <0.02). In both NJ and J-A groups, expression of numerous tissue biomarkers separated normal from CaP tissue, including markers for apoptosis (Bcl-2, caspase-3), growth factor receptors (epidermal growth factor receptor), racemase, 5-lipoxygenase, kinase inhibition (p27), and cell proliferation (Ki-67; all P <0.02). Furthermore, within both normal and CaP tissues, caspase-3 and 5-lipoxygenase were expressed more in NJ than in J-A men (P <0.01). Nuclear morphometry showed that the chromatin in each of the four groups (normal versus CaP, NJ versus J-A) was different (area under the curve 85% to 94%, P <0.01), despite fundamental genetic homogeneity. CONCLUSIONS: NJ and J-A men, products of similar genetics but differing environments, were shown to have differences in body composition that could influence CaP evolution. The CaP specimens from the NJ and J-A men were histologically similar, but tissue biomarker expression, especially of lipoxygenase and the caspase family, suggested differing mechanisms of carcinogenesis. Differences in nuclear morphometry suggested the additional possibility of gene-nutrient interactions.

Adenocarcinoma↗

PubMed2004

Microvessel density as a molecular marker for identifying high-grade prostatic intraepithelial neoplasia precursors to prostate cancer.

BACKGROUND: Existing clinical data have shown that high-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precursor to prostate cancer (CaP). Criteria to distinguish HGPIN that progress to CaP from those that do not remain poorly defined. Our objective was to evaluate microvessel density as a molecular marker for distinguishing HGPINs that have the potential of progressing to cancer. MATERIALS AND METHODS: Human prostatic tissue samples were collected randomly from 50 prostatectomy and cystoprostatectomy patients. Formalin-fixed and paraffin-embedded sections were used for immunohistochemical localization of rabbit anti-human von Willebrand factor VIII (vWF) IgG, mouse anti-high molecular weight cytokeratin 34BE-12 in basal cells, and mouse anti-heparan sulphate proteoglycan (HSPG) IgGs in basement membranes associated with benign prostatic hyperplasia (BPH), PIN associated with some BPH (isolated PIN), and PIN associated with CaP. RESULTS: Analysis of immunostaining data showed that PINs could be categorized according to their distributions within and outside 2 standard deviations (SD) of the mean for microvessel density. The average number of microvessels was significantly higher (P < 0.0001) in PINs associated with Gleason score 7 tumors than those associated with Gleason scores 4-6 (P < 0.1328) or 8 and 9 tumors (P < 0.1708). Morphologically, PINs within 2 SD were composed of low- and high-grade type, whereas those outside 2 SD of microvessel density were predominantly of high-grade type. Cytokeratin and HSPG localization patterns also showed differences in PINs found within and outside 2 SD of microvessel density. We found localization of cytokeratin 34BE-12 in basal cells of specimens with BPH alone, isolated PIN, and PIN associated with CaP within 2 SD, whereas many PINs outside 2 SD showed disruptions in cytokeratin localization. The basement membranes of PINs within 2 SD of microvessel density were relatively intact, whereas those outside 2 SD were fragmented. CONCLUSIONS: Our immunostaining data indicates that once HGPIN is found in the initial prostatic biopsy, it should be evaluated for microvessel density by localization of vWF. Our data indicate that characteristics of HGPIN can be augmented by evaluations of cytokeratin and HSPG molecular markers to assess the potential of HGPIN progression to malignancy. When biopsy samples show HGPIN with increased microvessel density and disrupted cytokeratin and HSPG markers, the patient may be a candidate for repeat biopsy. Since our study is limited to 50 prostate tissue samples, we emphasize that our conclusion is tentative and ought to be confirmed in a study with a larger sample size. This is the first report to show that microvessel density may distinguish HGPIN that is a precursor to prostate cancer.

Aged↗

PubMed2004

Molecular genetic evidence for different clonal origins of epithelial and stromal components of phyllodes tumor of the prostate.

Phyllodes tumor of the prostate is a rare neoplasm, composed of epithelium-lined cysts and channels embedded in a variably cellular stroma. The pathogenetic relationship of the epithelium and stroma is unknown and whether each is a clonal neoplastic element is uncertain. We studied the clonality of phyllodes tumors from six patients who underwent either enucleation or transurethral resection as their initial treatment. This was followed by total prostatectomy in three of the patients. Laser-assisted microdissection was performed to extract epithelial and stromal components of phyllodes tumor from formalin-fixed, paraffin-embedded tissue. Polymerase chain reaction was used to amplify genomic DNA at specific loci on chromosome 7q31 (D7S522), 8p21.3-q11.1 (D8S133, D8S137), 8p22 (D8S261), 10q23 (D10S168, D10S571), 17p13 (TP53), 16q23.2 (D16S507), 12q11-12 (D12S264), 17q (D17S855), 18p11.22-p11 (D18S53), and 22q11.2 (D22S264). In each tumor, stroma and epithelium were analyzed separately. Gel electrophoresis with autoradiography was used to detect loss of heterozygosity. All tumors showed allelic loss in one or more loci of both the epithelial and stromal components. The frequency of allelic loss in the epithelial component was 2 of 5 (40%) at D7S522, 2 of 6 (33%) at D8S133, 1 of 5 (20%) at D8S137, 3 of 6 (50%) at D8S261, 4 of 4 (100%) at D10S168, 4 of 6 (67%) at TP53, 2 of 6 (33%) at D10S571, 6 of 6 (100%) at D16S507, 1 of 5 (20%) at D12S264, 1 of 6 (17%) at D17S855, 2 of 6 (33%) at D18S53, and 2 of 5 (40%) at D22S264. The frequency of allelic loss in the stromal component was 2 of 5 (40%) at D7S522, 1 of 6 (17%) at D8S133, 2 of 5 (40%) at D8S137, 3 of 6 (50%) at D8S261, 1 of 4 (25%) at D10S168, 3 of 6 (50%) at TP53, 2 of 6 (33%) at D10S571, 3 of 6 (50%) at D16S507, 1 of 5 (20%) at D12S264, 0 of 6 (0%) at D17S855, 1 of 6 (17%) at D18S53, and 0 of 5 (0%) at D22S264. The pattern of allelic loss is significantly different in both stroma and epithelium statistically; completely concordant allelic loss patterns were not seen in any tumor examined. Our data demonstrate that both epithelial and stromal components of phyllodes tumor of the prostate are clonal, supporting the hypothesis that both elements are neoplastic. While both epithelium and stroma are clonal proliferations, they appear to have different clonal origins.

Clone Cells↗

PubMed2004

High-grade prostatic intraepithelial neoplasia.

High-grade prostatic intraepithelial neoplasia (PIN) is now accepted as the most likely preinvasive stage of adenocarcinoma, almost two decades after its first formal description. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent invasive carcinoma. The only method of detection is biopsy; PIN does not significantly elevate serum prostate-specific antigen (PSA) concentration or its derivatives and cannot be detected by current imaging techniques, including ultrasound. Most patients with PIN will develop carcinoma within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype, which are similar to cancer rather than normal prostatic epithelium, indicating impairment of cell differentiation with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.

Black or African American↗

PubMed2004

Karyometry detects subvisual differences in chromatin organization state between cribriform and flat high-grade prostatic intraepithelial neoplasia.

This digital texture analysis-based study evaluates the chromatin organization state in flat and cribriform high-grade prostatic intraepithelial neoplasia (PIN), in the adjacent normal looking secretory epithelium and in the co-occurring adenocarcinoma. Digital texture analysis (karyometry) was carried out on hematoxylin and eosin-stained sections from 24 radical prostatectomy specimens with high-grade PIN (12 with flat and 12 with cribriform architectural pattern, respectively) and cancer. Quantification was also conducted on the normal looking secretory epithelium. Discriminant analysis and the nonsupervised learning algorithm P-index were used to identify suitable subsets of features useful for the discrimination and classification of pathological groups and to explore multivariate data structure in the pathological subgroups. The average nuclear abnormality increases monotonically from the histologically normal appearing secretory epithelium to high-grade PIN and to adenocarcinoma. The nuclei from the so-called perimeter compartment of the flat high-grade PIN lesions show a higher nuclear abnormality compared to the nuclei of the cribriform high-grade PINs. Discriminant analysis shows that flat and cribriform high-grade PINs fall into two populations. Processing by the nonsupervised learning algorithm P-index revealed the existence of three well-defined, distinct subpopulations of nuclei of different chromatin phenotype. In the flat high-grade PIN lesions the proportions of nuclei in the three subpopulations are 16.5% (low abnormality), 25.0% (mid abnormality) and 58.5% (high abnormality), respectively. In the cribriform high-grade PIN lesions, 100% of the nuclei are in the mid-abnormality subpopulation. These differences are also discernible in the co-occurring adenocarcinoma and the histologically normal appearing secretory epithelium. To conclude, karyometry and statistical analysis detect the existence of distinct cell subpopulations of different chromatin packaging and phenotype, with the nuclei from the flat high-grade PIN lesions, adjacent normal looking epithelium and co-occurring adenocarcinoma expressing a greater nuclear abnormality than in the specimens with cribriform high-grade PIN.

Cell Nucleus↗

PubMed2004

Needle-based ablation of renal parenchyma using microwave, cryoablation, impedance- and temperature-based monopolar and bipolar radiofrequency, and liquid and gel chemoablation: laboratory studies and review of the literature.

BACKGROUND AND PURPOSE: Small renal tumors are often serendipitously detected during the screening of patients for renal or other disease entities. Rather than perform a radical or partial nephrectomy for these diminutive lesions, several centers have begun to explore a variety of ablative energy sources that could be applied directly via a percutaneously placed needle-like probe. To evaluate the utility of such treatment for small renal tumors/masses, we compared the feasibility, regularity (consistency in size and shape), and reproducibility of necrosis produced in normal porcine kidneys by different modes of tissue ablation: microwaves, cold impedance-based and temperature-based radiofrequency (RF) energy (monopolar and bipolar), and chemical. Chemoablation was accomplished using ethanol gel, hypertonic saline gel, and acetic acid gel either alone or with simultaneous application of monopolar or bipolar RF energy. MATERIALS AND METHODS: A total of 107 renal lesions were created laparoscopically in 33 domestic pigs. Microwave thermoablation (N=12) was done using a Targis T3 (Urologix) 10F antenna. Cryoablation (N=16) was done using a single 1.5-mm probe or three 17F microprobes (17F SeedNet system; Galil Medical) (N=10 single probe and N=6 three probes); a double freeze cycle with a passive thaw was employed under ultrasound guidance. Dry RF lesions were created using custom-made 18-gauge single-needle monopolar probe with two or three exposed metal tips (GelTx) (N=12) or a single-needle bipolar probe (N=6) at 50 W of 510 kHz RF energy for 5 minutes. In addition, a multitine RF probe (RITA Medical Systems) was used in one set of studies (N=6). Both impedance- and temperature-based RF were evaluated. Chemoablation was performed with 95% ethanol (4 mL), 24% hypertonic saline (4 mL), and 50% acetic acid (4 mL) as single injections. In addition, chemoablation was tested with monopolar and bipolar RF (wet RF). Tissues were harvested 1 week after ablation for light microscopy. RESULTS: In 11 of the 15 ablation techniques, there was complete necrosis in all lesions; however, three ethanol gel lesions had skip areas, three hypertonic saline gel lesions showed no necrosis or injury, and one monopolar RF and one bipolar RF lesion showed skip areas. In contrast to impedance-based RF, heat-based RF (RITA) caused complete necrosis without skip areas. All cryolesions resulted in complete tissue necrosis, and cryotherapy was the only modality for which lesion size could be effectively monitored using ultrasound imaging. CONCLUSIONS: Cryoablation and thermotherapy produce well-delineated, completely necrotic renal lesions. The single-probe monopolar and bipolar RF produce limited areas of tissue necrosis; however, both are enhanced by using hypertonic saline, acetic acid, or ethanol gel. Hypertonic saline gel with RF consistently provided the largest lesions. Ethanol and hypertonic saline gels tested alone failed to produce consistent cellular necrosis at 1 week. In contrast, RITA using the Starburst XL probe produced consistent necrosis, while impedance-based RF left skip areas of viable tissue. Renal cryotherapy under ultrasound surveillance produced hypoechoic lesions, which could be reasonably monitored, while all other modalities yielded hyperechoic lesions the margins of which could not be properly monitored with ultrasound imaging.

Acetic Acid↗

PubMed2004

Phyllodes tumor of the prostate: long-term followup study of 23 cases.

PURPOSE: Phyllodes tumor of the prostate is a rare neoplasm of uncertain malignant potential. We studied a large series of phyllodes tumors to define the combination of histological features that are most useful for predicting patient outcome. MATERIALS AND METHODS: A total of 23 cases were obtained from our collective files from 1973 to 2002, and numerous clinical and pathological features were evaluated. A review of the reported cases of phyllodes tumor of the prostate was done. RESULTS: Patient age was 25 to 86 years (mean 55) and they usually presented with urinary obstructive symptoms and hematuria. The diagnosis was made in 18 tumors by transurethral resection, in 2 by enucleation, in 1 by tumor resection and in 2 by prostatectomy. We analyzed 5 histological features, including cellularity (scale of 1 to 3), cytologic atypia (scale of 1 to 3), the number of mitotic figures per 10 high power fields, the stroma-to-epithelium ratio (low or high) and necrosis (present or absent). This combination of features revealed that 14 cases were low grade phyllodes tumor, 7 were intermediate grade and 2 were high grade with the high grade cases characterized by increased cellularity, severe cytological atypia, more than 5 mitotic figures per 10 high power fields and a high stroma-to-epithelium ratio, indicating stromal overgrowth. Immunohistochemical studies of 8 tumors revealed consistent, intense cytoplasmic immunoreactivity in stromal cells for vimentin and actin, in luminal epithelial cells for prostate specific antigen, prostatic acid phosphatase and broad-spectrum keratin AE1/AE3, and in basal cells for high molecular weight keratin 34beta-E12. Recurrence was seen in 7 of 14 low grade tumors (50%) and in 1 patient low grade sarcoma emerged with subsequent distant metastases 14 years after initial diagnosis following 5 recurrences. Recurrence was seen in 6 of 7 intermediate grade tumors and low grade sarcoma emerged with subsequent abdominal wall metastases in 1 patient 11 years after initial diagnosis following 3 recurrences. The phyllodes tumor recurred in each patient with high grade tumors with a time to first recurrence of 6 and 0.2 years, respectively. Distant metastases developed in these 2 patients. CONCLUSIONS: Histological grading of prostatic phyllodes tumors is predictive of short-term outcome based on the combination of stromal cellularity, cytological atypia, number of mitotic figures and the stroma-to-epithelium ratio. However, these tumors usually recur after transurethral prostatic resection and they are often locally aggressive with time. The emergence of overt sarcoma and metastatic disease is more frequent than previously recognized. Complete resection at initial diagnosis appears to be indicated.

Acid Phosphatase↗

PubMed2004

'Vanishing' prostate cancer in radical prostatectomy specimens: incidence and long-term follow-up in 38 cases.

OBJECTIVE: To determine the incidence and long-term follow-up of the 'vanishing cancer' phenomenon, as complete sampling of some radical prostatectomy (RP) specimens reveals no residual cancer. MATERIALS AND METHODS: The Mayo Clinic prostate cancer RP database for 1966-1995 was searched for all cases in which there was no residual adenocarcinoma (pathological stage pT0). Each case was confirmed by a review of all tissue specimen slides. Various clinical and pathological features were evaluated, and the follow-up obtained for all patients. RESULTS: Among 6843 RPs there were 38 in which no residual cancer was identified despite careful sampling. There was a 10-fold decline in the incidence of this finding, from 2.1% before 1980 to 0.2% in 1993-95; this decline appeared to be caused by a decrease in the frequency of diagnosis of cancer by transurethral resection from > 10% before 1990 to < 2% in 1993-95. The mean (range) age of the patients was 63 (38-75) years. All cancers on biopsy or transurethral resection were well or moderately differentiated; clinical stages included T1a (42% of cases), T1b (45%) and T2 (13%). Six patients had a nerve-sparing RP, all after 1990. The mean follow-up was 9.6 (1.0-28.5) years, and there were no recurrences of cancer; the serum prostate specific antigen concentration remained at < 0.2 ng/mL in surviving patients. Six patients (16%) died from intercurrent disease. CONCLUSIONS: The incidence of 'vanishing cancer' declined between 1966 and 1995, probably as a result of the decline in the use of transurethral resection, occurring in 0.2% of RPs. The prognosis in such patients is excellent, indicating that there is no apparent clinical significance to microscopic foci of cancer that remain undetected after reasonably complete pathological sampling. The inability to identify cancer in a prostate removed for biopsy-confirmed carcinoma does not indicate technical failure.

Adult↗

PubMed2004

Hyperbaric oxygen does not accelerate latent in vivo prostate cancer: implications for the treatment of radiation-induced haemorrhagic cystitis.

OBJECTIVE: To assess the effects of hyperbaric oxygen (HBO2; often used to treat haemorrhagic cystitis, a known side-effect after radiation therapy for prostate cancer and with the potential to induce tumour angiogenesis and stimulate latent recurrence) on indolent in vivo prostate cancer in a murine model. MATERIALS AND METHODS: Human prostate LNCaP cells were injected into 60 severe combined-immunodeficient mice; of these 24 (40%) did not develop palpable tumours after 6 weeks. They were randomized to undergo 20 sessions of either HBO2 or normobaric air in standardized conditions, and observed for another 4 weeks before the histological assessment of any palpable tumours that developed. Analysis of developed LNCaP tumours included tumour volume, microvessel density, MIB-1, p53, p27 and racemase staining intensity. RESULTS: HBO2 was associated with less prostate tumour progression than normobaric air (P = 0.26). During HBO2 therapy, 10 mice remained free of palpable tumours, compared with seven controls (P = 0.30). On evaluation during the 4 weeks after therapy, six mice treated with HBO2 remained free of palpable tumours, vs eight of the controls (P = 0.17). There was tumour invasion and necrosis in a two of six and four of the HBO2 group during and after therapy, respectively, vs five and seven of the controls. Tumour microvessel density, proliferative index, differentiation and apoptosis markers were similar in both groups. CONCLUSIONS: HBO2 does not accelerate the growth of indolent prostate cancer in a murine model, suggesting that it does not increase the risk of residual prostate cancer reactivation when it is used to manage radiation-induced haemorrhagic cystitis in patients treated by pelvic radiotherapy for prostate cancer.

Animals↗

PubMed2004

Does finasteride alter the pathology of the prostate and cancer grading?

All forms of androgen-deprivation therapy, including finasteride, induce distinctive histologic changes in benign and neoplastic prostatic epithelial cells, including cytoplasmic clearing, nuclear and nucleolar shrinkage, and chromatin condensation. Treated cancer has a significantly higher architectural (Gleason) grade, lower nuclear grade, and smaller nucleolar diameter than untreated controls, creating the potential for grading bias. Recognition of these changes may be difficult in needle biopsies and lymph node metastases with treated cancer because of the subtle infiltrative pattern and inconspicuous nucleoli. The effects of finasteride may be less pronounced than other forms of therapy with variable distribution throughout the prostate; further, there may be greater sensitivity of low and intermediate-grade cancer than high-grade cancer. The Gleason grading system for cancer should not be used after finasteride treatment as it is not validated in this setting and is likely to overestimate the biologic potential of high-grade cancer observed after therapy. Chemoprevention trials with agents such as finasteride that alter morphology should not rely on cancer grading as a secondary endpoint owing to grading bias.

5-alpha Reductase Inhibitors↗

PubMed2004

High-grade prostatic intraepithelial neoplasia.

High-grade prostatic intraepithelial neoplasia is considered the most likely precursor of prostatic carcinoma. The only method of detection is biopsy; prostatic intraepithelial neoplasia (PIN) does not significantly elevate serum prostate-specific antigen concentration and cannot be detected by ultra-sonography. The incidence of PIN in prostate biopsies averages 9% (range, 4%-16%), representing 115,000 new cases of PIN diagnosed each year in United States. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeated biopsy for concurrent or subsequent invasive carcinoma. Carcinoma will develop in most patients with PIN within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype that are intermediate between normal prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.

Journal Article↗

PubMed2003

Intraepithelial and stromal lymphocytes in the normal human prostate.

BACKGROUND: The distribution and significance of lymphocytes in the normal human prostate is uncertain. It may be important as a determinant of the immune response, playing a role in hyperplasia and carcinogenesis. METHODS: We studied 28 normal autopsy prostates from patients between 1 and 64 years of age. Cases with nodular hyperplasia, intraepithelial neoplasia, cancer, and florid prostatitis were excluded. Each prostate was routinely processed to paraffin and immunohistochemically stained for CD20, CD45, and CD45RO. Three frozen samples obtained from these cases were stained for CD8 and CD4. One low power field (25 x magnification, 50 mm(2)) was randomly chosen for examination from each anatomic zone of the prostate, namely the peripheral, transition, and central zone. Lymphocytes were visually counted in the stroma and epithelium of each zone. Lymphocyte counts were converted to number of cells per square millimeter based on the area of the slide per field and the percentage of field that was glandular. RESULTS: Stromal lymphocytes were more numerous than epithelial lymphocytes (mean, 7.32 and 2.04 cells/mm(2), respectively). They were mostly T cells (stromal lymphocytes: 93% CD45RO +; epithelial lymphocytes: 99% CD45RO +). Helper/inducer (CD4 +) T cells predominated in the stroma, whereas those in epithelium were chiefly cytotoxic/suppressor (CD8 +). No difference was found in the number of stromal and epithelial T or B cells according to patient age, race, or location within the prostate (peripheral, central, and transition zones) (all P > 0.05), although the number of lymphocytes in the peripheral zone tended to exceed that in the other zones after correcting for gland:stroma ratio. CONCLUSIONS: The immune response in the prostate is primarily cell-mediated. Cell distribution is constant according to patient age, race, and anatomic zonal location within the prostate. The greatest concentration is in the stroma with a small but significant number of intraepithelial cells. The inverted CD4/CD8 ratio in the intraepithelial compartment suggests that cytotoxic/suppressor T cells are the first line of defense against luminal foreign agents reaching the prostate through retrograde flow.

Adolescent↗

PubMed2003

Effects of dietary selenium supplementation on DNA damage and apoptosis in canine prostate.

The trace mineral selenium inhibits cancer development in a variety of experimental animal models. We used an in vivo canine model to evaluate the effects of dietary selenium supplementation on DNA damage in prostate tissue and on apoptosis in prostate epithelial cells. Sexually intact elderly male beagle dogs were randomly assigned to receive an unsupplemented diet (control group) or diets that were supplemented with selenium (treatment group), either as selenomethionine or as high-selenium yeast at 3 micro g/kg or 6 micro g/kg body weight per day for 7 months. The extent of DNA damage in prostate cells and in peripheral blood lymphocytes, as determined by the alkaline comet assay, was lower among the selenium-supplemented dogs than among the control dogs (prostate P<.001; peripheral blood lymphocytes P =.003; analysis of variance) but was not associated with the activity of the antioxidant enzyme glutathione peroxidase in plasma. The median number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive (i.e., apoptotic) prostate epithelial cells was 3.7 (interquartile range = 1.1-7.6) for the selenium-supplemented dogs and 1.7 (interquartile range = 0.2-2.8) for the control dogs ( P =.04, Mann-Whitney U test). These data suggest that dietary selenium supplementation decreases DNA damage and increases epithelial cell apoptosis within the aging canine prostate.

Animals↗

PubMed2003

Subvisual changes in chromatin organization state are detected by karyometry in the histologically normal urothelium in patients with synchronous papillary carcinoma.

This study analyzed the chromatin organization state in histologically normal urothelium in patients with synchronous papillary carcinoma using digital texture analysis. The quantitative evaluation was carried out on hematoxylin and eosin-stained sections from 17 cases of urothelial papillary carcinoma in which a simultaneous biopsy specimen featuring histologically normal urothelium was available. Five bladder biopsy specimens of histologically normal urothelium from patients with prostate pathology in whom cystoscopy revealed a normal bladder mucosa were also analyzed. Karyometry showed that the 17 cases of papillary carcinoma, morphologically classified according to the 1973 World Health Organization scheme, belonged to a continuous spectrum or trend curve spanning grade 1 to grade 3. An abnormal pattern and distribution of the nuclear chromatin was seen in the normal-looking urothelium from the 17 bladders with papillary lesions. When this population was plotted along the trend curve, it occupied an intermediate position between the normal samples and samples from grade 1 carcinoma. When the nuclei were considered individually, the changes were detected only in a subpopulation of nuclei with chromatin alteration pointing toward that seen in grade 1 cases, even though distinct from them. In conclusion, karyometry can detect an abnormal chromatin pattern and distribution in the normal-looking urothelium adjacent to papillary carcinoma. Such alterations correspond to the so-called "malignancy-associated change."

Carcinoma, Papillary↗

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↗

PubMed2003

Gadolinium-enhanced MRI in the evaluation of minimally invasive treatments of the prostate: correlation with histopathologic findings.

OBJECTIVES: To explore the use of magnetic resonance imaging (MRI) with gadolinium enhancement as a noninvasive method to image the extent of ablation after minimally invasive treatment. Minimally invasive methods for ablating prostatic tissue have emerged as a viable option in the treatment of prostate disease. As these devices enter the mainstream of patient care, imaging methods that verify the exact location, extent, and pattern of the ablation are needed. METHODS: Nineteen patients with prostate cancer were evaluated. All received some type of minimally invasive treatment, post-treatment gadolinium-enhanced MRI sequences, and radical retropubic prostatectomy for histopathologic evaluation. Visual comparisons of gadolinium defects and areas of coagulation necrosis as seen on histopathologic evaluation were made by us. Volumetric and two-dimensional area measurements of the ablation lesions were also compared for correlation between the MRI and histopathologic results. RESULTS: Gadolinium-enhanced MRI could be matched to histopathologic findings by visual comparison in 17 of the 19 cases. Surgically distorted histopathologic specimens and a small periurethral lesion caused 2 patients to have MRI and histopathologic results that could not be matched. Complete volumetric measurements were available for 16 of the 19 patients and correlated strongly (r = 0.924). The two-dimensional area data for all patients also showed significant correlation (r = 0.886). CONCLUSIONS: Correlation with histopathologic findings showed gadolinium-enhanced MRI to be useful for determining the location, pattern, and extent of necrosis caused within the prostate by minimally invasive techniques. Gadolinium-enhanced MRI gives the urologist a useful tool to evaluate the effectiveness of new minimally invasive therapies.

Adenocarcinoma↗

PubMed2003

Contemporary pathology of prostate cancer.

In less than 20 years since the introduction of serum PSA and the spring-loaded 18-gauge prostatic biopsy needle, pathologists have adjusted to the limited tissue requirements of narrow needle specimens to apply criteria for diagnosis and grading of prostate cancer, borrowing from lessons learned from radical prostatectomies. Substantial gains have been made during this period in the understanding of precancerous lesions, mimics of malignancy, the criteria for minimal cancer, variants of cancer, and treatment-induced changes. The light microscopic findings remain the criterion standard for diagnosis against which all new techniques should be measured. Numerous findings have proven to be of value, including simple quantitation of histopathologic features, cancer volume, perineural invasion, and others.

Adenocarcinoma↗