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1.
Aliment Pharmacol Ther ; 43(8): 924-932, 2016 04.
Article in English | MEDLINE | ID: mdl-26890160

ABSTRACT

BACKGROUND: Helicobacter-negative gastritis has been increasingly reported. Molecular techniques as the polymerase chain reaction (PCR) may detect bacterial DNA in histologically negative gastritis. AIM: To evaluate of Helicobacter PCR in gastric biopsies for the daily diagnostics of Helicobacter-negative gastritis. METHODS: Over a 5-year period, routine biopsies with chronic gastritis reminiscent of Helicobacter infection, but negative by histology, were tested by using a H. pylori specific PCR. Subsequently, PCR-negative samples were re-evaluated using PCR for other Helicobacter species. RESULTS: Of the 9184 gastric biopsies, 339 (3.7%) with histological-negative gastritis and adequate material were forwarded to PCR analysis for H. pylori and 146 (43.1%) revealed a positive result. In 193 H. pylori DNA-negative biopsies, re-analysis using PCR primers for other Helicobacter species, revealed further 23 (11.9%) positive biopsies, including 4 (2.1%) biopsies with H. heilmannii sensu lato. PCR-positive biopsies showed a higher overall inflammatory score, more lymphoid follicles/aggregates and neutrophils (P < 0.05). No Helicobacter DNA was found in control biopsies of 48 patients with neither primer set (P < 0.0001). In 274 patients with an endoscopic description, detection of H. pylori DNA was associated with ulcers and erosions (P < 0.01). Over all, in 339 histologically-negative gastric biopsies, Helicobacter DNA was detected in 169 (49.9%) samples with at least one primer set. CONCLUSION: Molecular testing offers a sensitive and specific diagnosis to a selected group of patients, in whom adequate searches for bacteria by conventional histology have resulted in the unsatisfactory diagnosis of H. pylori-negative gastritis.


Subject(s)
Gastritis/microbiology , Helicobacter Infections/diagnosis , Polymerase Chain Reaction/methods , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy , DNA, Bacterial/analysis , Female , Helicobacter/isolation & purification , Helicobacter Infections/microbiology , Helicobacter pylori/genetics , Helicobacter pylori/isolation & purification , Humans , Male , Middle Aged , Young Adult
3.
Pathologe ; 33(4): 345-7, 2012 Jul.
Article in German | MEDLINE | ID: mdl-22555363

ABSTRACT

The number of interventional cardiovascular procedures has been rising steadily. Such procedures include the intravascular insertion of catheters and guide wires. These devices consist of a metallic core and coil that may be covered by hydrophilic coating to ease crossability and control for challenging lesions. We report two cases where insertion of a ChoICE® PT guide wire into the coronary artery led to embolization of the hydrophilic coating material with occlusion of small intramyocardial arteries.


Subject(s)
Angioplasty, Balloon, Coronary/adverse effects , Angioplasty, Balloon, Coronary/instrumentation , Coated Materials, Biocompatible/adverse effects , Coronary Stenosis/therapy , Coronary Thrombosis/pathology , Coronary Vessels , Embolism/pathology , Hydrophobic and Hydrophilic Interactions , Hypoxia-Ischemia, Brain/pathology , Myocardial Infarction/therapy , Pneumonia, Aspiration/pathology , Stents/adverse effects , Aged , Coronary Restenosis/pathology , Coronary Restenosis/therapy , Coronary Stenosis/pathology , Coronary Vessels/pathology , Fatal Outcome , Foreign-Body Reaction/pathology , Humans , Male , Middle Aged , Multiple Organ Failure/pathology , Myocardial Infarction/pathology , Myocardium/pathology , Retreatment
4.
Dis Markers ; 29(1): 47-53, 2010.
Article in English | MEDLINE | ID: mdl-20826917

ABSTRACT

AIMS: Programmed death-1 (PD-1) is expressed by germinal center-associated helper T-cells and acts as a negative regulator of the immune system. PD-1 is encountered on tumor cells of angioimmunoblastic T-cell lymphoma and is a postulated diagnostic marker in chronic lymphocytic leukemia (CLL/SLL). Recent data suggest prognostic importance of PD-1 in follicular lymphoma (FL). We assessed the diagnostic potential and the prognostic importance of PD-1 in B-cell lymphomas. METHODS: Distribution of PD-1+ lymphocytes in B-cell lymphomas was studied on 403 cases. Correlation with known biologic and clinical key data was performed. Prognostic cut-off scores were determined by receiver operating curve analysis. RESULTS: PD-1+ tumor-infiltrating lymphocytes were numerous in extranodal marginal zone lymphomas and FL. Their amount decreased from FL grade 1 to grade 3 and to FL with transformation to diffuse large B-cell lymphoma. An increased amount of PD-1 tumor-infiltrating lymphocytes above the prognostic cut-off score (> 2.8%) was a positive prognostic factor of disease-specific survival (DSS) in FL-patients. Five percent of the studied 66 CLL/SLL cases showed unequivocal PD-1 positivity of neoplastic cells. CONCLUSIONS: Increased number of PD-1+ tumor-infiltrating lymphocytes is associated with significantly improved DSS in FL and may be useful to predict its heterogeneous clinical behavior. PD-1 has probably limited diagnostic value for primary histopathological CLL/SLL diagnostics.


Subject(s)
Antigens, CD/metabolism , Apoptosis Regulatory Proteins/metabolism , Biomarkers, Tumor/metabolism , Lymphoma, B-Cell/metabolism , Adult , Aged , Female , Humans , Immunohistochemistry , Lymphocytes, Tumor-Infiltrating/metabolism , Lymphoma, B-Cell/pathology , Male , Middle Aged , Prognosis , Programmed Cell Death 1 Receptor
5.
J Neurol ; 255(1): 77-88, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18204807

ABSTRACT

Several hereditary conditions affecting cerebral, retinal and systemic microvessels have recently been described. They include CADASIL, CRV, and HERNS. We here report on a variant form of a hereditary systemic angiopathy (HSA) affecting two generations of a Caucasian family. Clinical symptoms of HSA appear in the mid-forties and are characterized by visual impairment, migraine-like headache, skin rash, epileptic seizures, progressive motor paresis and cognitive decline. Late symptoms include hepatic and renal failure. Retinal capillary microaneurysms and arteriolar tortuosity are associated with marked optic disc atrophy. Radiological hallmarks consist of multiple cerebral calcifications and tumor-like subcortical white matter lesions. Brain, peripheral nerve, muscle, kidney and colon biopsies have revealed a multi organ small vessel involvement with partly altered endothelium, perivascular inflammation and thrombotic microangiopathy. No curative therapeutic options are known for hereditary cerebral vasculopathies. The use of cyclophosphamide, azathioprine and methotrexate was of no benefit in our cases of HSA. Early diagnosis of hereditary systemic angiopathies is important in order to prevent patients from repetitive invasive diagnostic measures and to avoid the use of inappropriate and potentially harmful drugs.


Subject(s)
Cerebral Arterial Diseases/pathology , Kidney Diseases/pathology , Liver Diseases/pathology , Retinal Diseases/pathology , Vascular Diseases/pathology , Adult , Aged , Brain/blood supply , Brain/pathology , Brain/physiopathology , Calcinosis/pathology , Calcinosis/physiopathology , Cerebral Arterial Diseases/physiopathology , Cerebral Arteries/pathology , Cerebral Arteries/physiopathology , Disease Progression , Early Diagnosis , Female , Humans , Immunosuppressive Agents/therapeutic use , Kidney Diseases/physiopathology , Liver Diseases/physiopathology , Liver Failure/pathology , Liver Failure/physiopathology , Male , Microcirculation/pathology , Microcirculation/physiopathology , Middle Aged , Renal Insufficiency/pathology , Renal Insufficiency/physiopathology , Retinal Artery/pathology , Retinal Artery/physiopathology , Retinal Diseases/physiopathology , Syndrome , Treatment Outcome , Vascular Diseases/physiopathology , Vasculitis/pathology , Vasculitis/physiopathology , Viscera/blood supply , Viscera/pathology , Viscera/physiopathology
6.
Water Sci Technol ; 48(1): 57-65, 2003.
Article in English | MEDLINE | ID: mdl-12926621

ABSTRACT

The technology of urine separation and the recycling of anthropogenic nutrients as fertilizer in agriculture are considered as major innovations to improve the sustainability of today's urban wastewater management. The acceptance of consumers will be key for the introduction of the new technology. Citizens will have to make important decisions in their role as tenants and owners of houses and as consumers buying products fertilized with urine. Consumer attitudes towards the new technology were explored in a number of citizen focus groups in Switzerland. Focus groups are deliberate, moderated group discussions with informed citizens on a certain topic. The information was provided by a computer based information system specifically designed for this purpose. The acceptance of individual citizens for the new technology proved to be quite high. The majority of the citizens expressed their willingness to move into an apartment with NoMix toilets and to buy food fertilized with urine. However, they were not willing to accept additional financial costs or efforts. Arguments related to long-term sustainability (closing nutrient cycles) were of less importance than arguments that relate directly to the effects of micropollutants on human and ecosystem health. For the introduction of the new technology on a wide scale it will thus be crucial to explore the fate and effects of micropollutants.


Subject(s)
Agriculture , Conservation of Natural Resources , Public Opinion , Urine/chemistry , Community Participation , Ecosystem , Focus Groups , Humans , Public Health , Technology Transfer , Waste Disposal, Fluid
7.
Am J Pathol ; 159(6): 2089-94, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11733359

ABSTRACT

Gain of the long arm of chromosome 8 (8q) is one of the most common gains found in the advanced prostate cancer by comparative genomic hybridization. We have previously identified a putative target gene for the 8q gain, EIF3S3, that encodes a p40 subunit of eukaryotic translation initiation factor 3 (eIF3). Here, we studied the frequency of the EIF3S3 amplification in different stages of prostate cancer and co-amplification of EIF3S3 and oncogene MYC. In addition, prognostic utility of the EIF3S3 copy number alteration was evaluated. The analyses were done with fluorescence in situ hybridization and tissue microarray technology. High-level amplification of EIF3S3 was found in 11 of 125 (9%) of pT1/pT2 tumors, 12 of 44 (27%) of pT3/pT4 tumors, and 8 of 37 (22%) of lymph node metastases as well as in 26 of 78 (33%) and 15 of 30 (50%) of hormone refractory locally recurrent tumors and metastases, respectively. The amplification was associated with high Gleason score (P < 0.001). One of the 79 tumors with EIF3S3 amplification had only two copies of MYC, whereas all tumors with amplification of MYC had also amplification of EIF3S3 indicating common co-amplification of the genes. Gain of EIF3S3 was associated with poor cancer-specific survival in incidentally found prostate carcinomas (P = 0.023). In the analyses of prostatectomy-treated patients, the amplification was not statistically significantly associated with progression-free time. In conclusion, amplification of EIF3S3 gene is common in late-stage prostate cancer suggesting that it may be functionally involved in the progression of the disease.


Subject(s)
Peptide Initiation Factors/genetics , Prostatic Neoplasms/pathology , Aged , Aged, 80 and over , Eukaryotic Initiation Factor-3 , Gene Amplification , Gene Dosage , Humans , In Situ Hybridization, Fluorescence , Male , Middle Aged , Neoplasm Staging , Prostatic Neoplasms/genetics , Prostatic Neoplasms/mortality , Survival Analysis , Survival Rate
8.
Proc Natl Acad Sci U S A ; 98(8): 4575-80, 2001 Apr 10.
Article in English | MEDLINE | ID: mdl-11287641

ABSTRACT

The ANX7 gene is located on human chromosome 10q21, a site long hypothesized to harbor a tumor suppressor gene(s) (TSG) associated with prostate and other cancers. To test whether ANX7 might be a candidate TSG, we examined the ANX7-dependent suppression of human tumor cell growth, stage-specific ANX7 expression in 301 prostate specimens on a prostate tissue microarray, and loss of heterozygosity (LOH) of microsatellite markers at or near the ANX7 locus. Here we report that human tumor cell proliferation and colony formation are markedly reduced when the wild-type ANX7 gene is transfected into two prostate tumor cell lines, LNCaP and DU145. Consistently, analysis of ANX7 protein expression in human prostate tumor microarrays reveals a significantly higher rate of loss of ANX7 expression in metastatic and local recurrences of hormone refractory prostate cancer as compared with primary tumors (P = 0.0001). Using four microsatellite markers at or near the ANX7 locus, and laser capture microdissected tumor cells, 35% of the 20 primary prostate tumors show LOH. The microsatellite marker closest to the ANX7 locus showed the highest rate of LOH, including one homozygous deletion. We conclude that the ANX7 gene exhibits many biological and genetic properties expected of a TSG and may play a role in prostate cancer progression.


Subject(s)
Annexin A7/genetics , Genes, Tumor Suppressor , Prostatic Neoplasms/genetics , Cell Division/genetics , Chromosomes, Human, Pair 10 , Genetic Markers , Humans , Immunohistochemistry , Loss of Heterozygosity , Male , Oligonucleotide Array Sequence Analysis , Polymerase Chain Reaction , Polymorphism, Genetic , Prostatic Neoplasms/pathology
9.
Prostate ; 46(3): 184-90, 2001 Feb 15.
Article in English | MEDLINE | ID: mdl-11170146

ABSTRACT

BACKGROUND: DNA sequence amplifications are involved in the progression of many tumor types, and have also been found in advanced prostate cancer. The aim of this study was to detect new loci of DNA amplifications in prostate cancer. METHODS: Comparative genomic hybridization (CGH) was used for whole genome screening of DNA sequence copy number alterations in 27 advanced prostate cancers. RESULTS: The most prevalent changes were losses of 8p, 13q (52%, each), 6q (48%), 18q (37%), 5q (30%), 2q, 4q and 16q (26%, each), and gains of 8q (48%), Xq (40%), and Xp (26%). In addition, 16 high-level amplifications were found. These included Xq12 (five), 8q24 (two), and 11q13 (one) with known putative target genes (androgen receptor, MYC and Cyclin D1), and 1q21-25 (three), 10q22 (two), 17q23-24 (two), and 8q21 (one) where the target genes remain unknown. CONCLUSIONS: High-level amplifications at different chromosomal sites occur in advanced prostate cancer. The detection of amplified chromosomal regions may serve as a starting point to discover novel oncogenes involved in prostate cancer progression.


Subject(s)
DNA, Neoplasm/genetics , Gene Amplification , Prostatic Neoplasms/genetics , Aged , Aged, 80 and over , Chromosome Deletion , Disease Progression , Humans , Male , Middle Aged , Nucleic Acid Hybridization , Prostatic Neoplasms/pathology
10.
Urology ; 56(5): 880-5, 2000 Nov 01.
Article in English | MEDLINE | ID: mdl-11068328

ABSTRACT

OBJECTIVES: The genetic basis underlying prostate cancer development and progression is poorly understood. The primary aim of this study was to identify chromosomal regions important for progression in clinically localized prostate cancer removed by radical prostatectomy. METHODS: Comparative genomic hybridization was used for whole genome screening of DNA sequence copy number alterations in 28 pathologically organ-confined tumors (pT2) and 28 tumors with infiltration of the seminal vesicles (pT3b). RESULTS: Comparative genomic hybridization analysis showed on average 2.0 +/- 2.4 chromosomal alterations per tumor with more frequent losses (mean 1.3 +/- 1.8) than gains (mean 0.7 +/- 1.0). The percentage of tumors without alterations was higher in Stage pT2 (21%) than in Stage pT3b (50%). Losses of 8p (21%), 13q (21%), 5q (14%), 16q (14%), and 18q (13%) and gains of Xq (21%) and 8q (9%) were the most prevalent changes. Distinct regional alterations included minimal overlapping regions of loss at 5q13-q21, 6q14-q21, and 18q21-qter. There was only a small increase in the number of alterations from Stage pT2 to Stage pT3b (mean 1.6 +/- 2.3 versus 2.5 +/- 2.4). However, two individual alterations-gain of 8q and loss of 18q-were significantly more frequent in Stage pT3b than in Stage pT2 prostate cancer (P = 0.02 and P = 0.04, respectively), suggesting that genes in these regions may be important for prostate cancer progression. CONCLUSIONS: The detection of chromosome 8q gains and 18q losses and the identification of the corresponding target genes could become a molecular tool for better characterization of clinically localized prostate cancer.


Subject(s)
Chromosomes, Human, Pair 18/genetics , Chromosomes, Human, Pair 8/genetics , DNA, Neoplasm/analysis , Prostatic Neoplasms/genetics , Chromosome Aberrations/genetics , Chromosomes, Human, Pair 13/genetics , Chromosomes, Human, Pair 5/genetics , Chromosomes, Human, Pair 6/genetics , DNA Probes , Disease Progression , Humans , Male , Neoplasm Staging , Prostatectomy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , X Chromosome/genetics
11.
Cancer Res ; 60(21): 6111-5, 2000 Nov 01.
Article in English | MEDLINE | ID: mdl-11085535

ABSTRACT

NKX3.1 is a prostate-specific homeobox gene located on chromosome 8p21. In the mouse, Nkx3.1 has growth-suppressive and differentiating effects on prostatic epithelium. Mutations of the coding region of NKX3.1 were not found in human prostate cancer, failing to support the notion that NKX3.1 was a tumor suppressor gene. To study the expression o NKX3.1 protein in human tissues and prostate cancer, we derived a rabbit antiserum against purified recombinant NKX3.1. Among normal human tissues, NKX3.1 expression was seen in testis, in rare pulmonary mucous glands, and in isolated regions of transitional epithelium of the ureter. NKX3.1 was uniformly expressed in nuclei of normal prostate epithelial cells in 61 histological sections from radical prostatectomy specimens. We analyzed 507 samples of neoplastic prostate epithelium, most of which were contained on a tissue microarray that contained samples from different stages of prostatic neoplasia. We observed complete loss of NKX3.1 expression in 5% of benign prostatic hyperplasias, 20% of high-grade prostatic intraepithelial neoplasias, 6% of T1a/b samples, 22% of T3/4 samples, 34% of hormone-refractory prostate cancers, and 78% of metastases. Our data show that NKX3.1 expression is highly, but not exclusively, specific for the prostate. Loss of NKX3.1 expression is strongly associated with hormone-refractory disease and advanced tumor stage in prostate cancer (P < 0.0001).


Subject(s)
Gene Silencing , Homeodomain Proteins/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Transcription Factors/genetics , Animals , Disease Progression , Epithelium/metabolism , Gene Expression , Gene Expression Regulation, Neoplastic , Genes, Tumor Suppressor , Homeodomain Proteins/biosynthesis , Homeodomain Proteins/immunology , Humans , Immune Sera , Immunohistochemistry , Male , Prostatic Neoplasms/metabolism , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Rabbits , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunology , Recombinant Fusion Proteins/isolation & purification , Testis/metabolism , Transcription Factors/biosynthesis , Transcription Factors/immunology
12.
Hum Pathol ; 31(5): 578-83, 2000 May.
Article in English | MEDLINE | ID: mdl-10836297

ABSTRACT

The prognosis of prostate cancer is mainly determined by the presence or absence of metastases. Nevertheless, the metastatic pathways in prostate cancer are not entirely understood. Among 19,316 routine autopsies performed from 1967 to 1995 on men older than 40 years of age, the reports from those 1,589 (8.2%) with prostate cancer were analyzed. Hematogeneous metastases were present in 35% of 1,589 patients with prostate cancer, with most frequent involvement being bone (90%), lung (46%), liver (25%), pleura (21%), and adrenals (13%). Several lines of evidence suggested the existence of a backward metastatic pathway through veins from the prostate to the spine in addition to classical hematogeneous tumor spread via the vena cava. First, there was an inverse relationship between spine and lung metastases, suggesting that metastasis to the spine is independent of lung metastasis. Second, the maximum frequency of spine involvement occurred in smaller tumors (4 to 6 cm) as compared with the maximum spread to lung (6 to 8 cm) and liver (>8 cm), suggesting that spine metastases precede lung and liver metastases in many prostate cancers. Third, there was a gradual decrease in spine involvement from the lumbar to the cervical level (97% v 38%), which is consistent with a subsequent upward metastatic spread along spinal veins after initial lumbar metastasis. The results of this study show that bone, lung, and liver are the most frequent sites of distant prostate cancer metastases. Besides the cava-type of metastasis through lung passage, there are strong arguments for the existence and clinical significance of a backward venous spread to the spine, which is likely to occur early in the metastatic process.


Subject(s)
Prostatic Neoplasms/secondary , Adult , Aged , Aged, 80 and over , Bone Neoplasms/secondary , Cadaver , Humans , Liver Neoplasms/secondary , Lung Neoplasms/secondary , Lymphatic Metastasis , Male , Middle Aged , Spinal Neoplasms/secondary
13.
J Natl Cancer Inst ; 91(20): 1758-64, 1999 Oct 20.
Article in English | MEDLINE | ID: mdl-10528027

ABSTRACT

BACKGROUND: The molecular mechanisms underlying the progression of prostate cancer during hormonal therapy have remained poorly understood. In this study, we developed a new strategy for the identification of differentially expressed genes in hormone-refractory human prostate cancer by use of a combination of complementary DNA (cDNA) and tissue microarray technologies. METHODS: Differences in gene expression between hormone-refractory CWR22R prostate cancer xenografts (human prostate cancer transplanted into nude mice) and a xenograft of the parental, hormone-sensitive CWR22 strain were analyzed by use of cDNA microarray technology. To validate the data from cDNA microarrays on clinical prostate cancer specimens, a tissue microarray of specimens from 26 prostates with benign prostatic hyperplasia, 208 primary prostate cancers, and 30 hormone-refractory local recurrences was constructed and used for immunohistochemical detection of protein expression. RESULTS: Among 5184 genes surveyed with cDNA microarray technology, expression of 37 (0.7%) was increased more than twofold in the hormone-refractory CWR22R xenografts compared with the CWR22 xenograft; expression of 135 (2.6%) genes was reduced by more than 50%. The genes encoding insulin-like growth factor-binding protein 2 (IGFBP2) and 27-kd heat-shock protein (HSP27) were among the most consistently overexpressed genes in the CWR22R tumors. Immunohistochemical analysis of tissue microarrays demonstrated high expression of IGFBP2 protein in 100% of the hormone-refractory clinical tumors, in 36% of the primary tumors, and in 0% of the benign prostatic specimens (two-sided P =.0001). Overexpression of HSP27 protein was demonstrated in 31% of the hormone-refractory tumors, in 5% of the primary tumors, and in 0% of the benign prostatic specimens (two-sided P =.0001). CONCLUSIONS: The combination of cDNA and tissue microarray technologies enables rapid identification of genes associated with progression of prostate cancer to the hormone-refractory state and may facilitate analysis of the role of the encoded gene products in the pathogenesis of human prostate cancer.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , DNA, Complementary/drug effects , DNA, Neoplasm/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Animals , DNA, Complementary/analysis , DNA, Neoplasm/analysis , Heat-Shock Proteins/analysis , Heat-Shock Proteins/genetics , Humans , Immunohistochemistry , Insulin-Like Growth Factor Binding Protein 2/analysis , Insulin-Like Growth Factor Binding Protein 2/genetics , Male , Mice , Mice, Nude , Neoplasm Recurrence, Local , Prostatic Hyperplasia/genetics , Prostatic Neoplasms/chemistry , Reverse Transcriptase Polymerase Chain Reaction , Transplantation, Heterologous , Treatment Failure
14.
Cancer Res ; 59(4): 803-6, 1999 Feb 15.
Article in English | MEDLINE | ID: mdl-10029066

ABSTRACT

Prostate cancer development and progression is driven by the accumulation of genetic changes, the nature of which remains incompletely understood To facilitate high-throughput analysis of molecular events taking place in primary, recurrent, and metastat prostate cancer, we constructed a tissue microarray containing small 0.6-mm cylindrical samples acquired from 371 formalin-fixed blocks, including benign prostatic hyperplasia (n = 32) and primary tumors (n = 223), as well as both locally recurrent tumors (n = 54) and metastases (n = 62) from patients with hormone-refractory disease. Fluorescence in situ hybridization (FISH) was applied to the analysis of consecutive tissue microarray sections with probes for five different genes. High-level (> or =3X) amplifications were very rare (<2%) in primary prostate cancers However, in metastases from patients with hormone-refractory disease, amplification of the androgen receptor gene was seen in 22%, MYC in 11%, and Cyclin-D1 in 5% of the cases. In specimens from locally recurrent tumors, the corresponding percentages were 23, 4, and 8%. ERBB2 and NMYC amplifications were never detected at any stage of prostate cancer progression. In conclusion, FISH to tissue microarray sections enables high-throughput analysis of genetic alterations contributing to cancer development and progression. Our results implicate a role for amplification of androgen receptor in hormonal therapy failure and that of MYC in the metastatic progression of human prostate cancer.


Subject(s)
Gene Amplification , In Situ Hybridization, Fluorescence , Prostatic Neoplasms/genetics , Cyclin D1/genetics , Genes, erbB-2 , Genes, myc , Humans , Male , Receptors, Androgen/genetics
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