Carcinoma ; genetics ; metabolism ; pathology ; surgery ; China ; Humans ; Male ; Oncogene Proteins, Fusion ; genetics ; Prostatic Hyperplasia ; genetics ; metabolism ; pathology ; surgery ; Prostatic Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Proto-Oncogene Proteins c-ets ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Serine Endopeptidases ; genetics ; metabolism

AIMTo evaluate androgen receptor (AR) expression in clinically localized prostate cancer (PCa).

METHODSSpecimens were studied from 232 patients who underwent radical prostatectomy for clinically localized prostatic adenocarcinoma without neoadjuvant hormonal therapy or chemotherapy at our institution between November 2001 and June 2005. Immunohistochemical study was performed using an anti-human AR monoclonal antibody AR441. The mean AR density in the hot spots of different histological areas within the same sections were compared and the correlation of malignant epithelial AR density with clinicopathological parameters such as Gleason score, tumor, nodes and metastases (TNM) stage and pre-treatment prostate-specific antigen (PSA) value was assessed.

RESULTSAR immunoreactivity was almost exclusively nuclear and was observed in tumor cells, non-neoplastic glandular epithelial cells and a proportion of peritumoral and interglandular stromal cells. Mean percentage of AR-positive epithelial cells was significantly higher in cancer tissues than that in normal prostate tissues (mean +/- SD, 90.0% +/- 9.3% vs. 85.3 +/- ?9.7%, P < 0.001). The histological score yielded similar results. The percentage of AR immunoreactive prostatic cancer nuclei and histological score were not correlated with existing parameters such as Gleason score, tumor, nodes and metastases stage and pre-treatment PSA value in this surgically treated cohort.

CONCLUSIONThe results of the present study suggest that there may be limited clinical use for determining AR expression (if evaluated in hot spots) in men with localized PCa.

Adenocarcinoma ; genetics ; pathology ; surgery ; Aged ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Paraffin Embedding ; Prostate-Specific Antigen ; analysis ; metabolism ; Prostatectomy ; Prostatic Neoplasms ; genetics ; pathology ; surgery ; Receptors, Androgen ; biosynthesis ; genetics

The most appropriate time to introduce androgen deprivation therapy for prostate cancer remains controversial. Our aim was to evaluate the effects of early versus delayed surgical castration on prostate cancer progression and survival in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. TRAMP mice were randomly divided into three groups: the early castration group (on which castration was performed at the age of 4 weeks), the delayed castration group (on which castration was performed when abdominal tumours could be palpated), and the sham-castrated group. Mice were monitored daily throughout their lives until cancer-related death or the development of an obviously moribund appearance, at which time the individual mouse was killed. Androgen receptor expression in prostate tumours was also evaluated. The results shows that the average lifespan in early castration, delayed castration and sham-castrated groups were 54.1 weeks, 59.9 weeks and 39.1 weeks, respectively. Both early castration and delayed castration conferred a statistically significant survival advantage when compared with the sham-castrated group (P<0.001). However, the difference in lifespan between the early castration group and the delayed castration group was not statistically significant (P=0.85). The increase in lifespan in the TRAMP mice that received either early or delayed castration correlated with lower G/B value (genitourinary tract weight/body weight) at death than the sham-castrated mice. In conclusion, early and delayed castrations in TRAMP mice prolonged survival to a similar extent. This finding may provide a guide for clinical practice in prostate cancer therapy.
Adenocarcinoma ; mortality ; pathology ; surgery ; Animals ; Body Weight ; Disease Models, Animal ; Kaplan-Meier Estimate ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Orchiectomy ; Organ Size ; Prostate ; metabolism ; pathology ; surgery ; Prostatic Neoplasms ; mortality ; pathology ; surgery ; Receptors, Androgen ; metabolism ; Time Factors ; Transgenes ; genetics

Aneuploidy ; Gene Rearrangement ; Glutathione S-Transferase pi ; metabolism ; Humans ; Male ; Methylation ; Neoplasm Grading ; Neoplasm Staging ; Neoplasms, Multiple Primary ; genetics ; metabolism ; pathology ; surgery ; Oncogene Proteins, Fusion ; genetics ; Prostate-Specific Antigen ; metabolism ; Prostatic Intraepithelial Neoplasia ; genetics ; pathology ; Prostatic Neoplasms ; genetics ; metabolism ; pathology ; surgery

OBJECTIVETo clarify the significance of micrometastases in pelvic lymph nodes in patients with neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP).

METHODSTwenty-one patients with clinically localized prostate cancer who received NHT between August 2007 and March 2010 were observed. The patients were clarified into four groups: pathological examination was positive (group A), real-time PCR examination targeting prostate specific antigen (PSA) mRNA and prostate specific membrane antigen (PSMA) mRNA were positive (group B), pathological examination and real-time PCR examination targeting PSA mRNA and PSMA mRNA were both negative (group C), and the control group (group D). After a standard bipedal lymphangiography the films were reviewed carefully by an experienced radiologist. If positive lymph nodes were seen or suspected, a thin-walled 22 gauge needle were directed transabdominally under fluoroscopic control into the area of question and an aspirate was obtained. The expression of PSA and PSMA in aspirate were assessed by a fully quantitative real-time PCR. The specimens were regarded in which either PSA mRNA or PSMA mRNA were positive as showing the "presence of micrometastasis". Lymph node specimens were also stained immunohistochemically with an antibody PSA after RP.

RESULTSPathological examination detected lymph node metastases from 3 cases, and real-time PCR further identified lymph node micrometastases from 14 cases with no pathological evidence of nodal involvement. The expression level of PSA mRNA and PSMA mRNA were statistically significant in patients with histological confirmed lymph node metastases and micrometastases detected by real-time PCR despite the lack of histological evidence, and the expression level of PSA mRNA and PSMA mRNA in aspirate were higher than the lymph node between the group A and group B.

CONCLUSIONSAlthough residual foci of atrophic prostate cancer cells in resected lymph nodes after NHT can be difficult to diagnose by pathological examination, the present results show the usefulness of quantitative real-time PCR targeting PSA and PSMA mRNA for detected micrometastatic tumour foci in pelvic lymph nodes from fine needle aspiration biopsy of lymph nodes before RP.

Aged ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; pathology ; Male ; Middle Aged ; Pelvis ; pathology ; Polymerase Chain Reaction ; methods ; Preoperative Care ; Prognosis ; Prostate-Specific Antigen ; genetics ; metabolism ; Prostatic Neoplasms ; pathology ; surgery ; RNA, Messenger ; genetics

OBJECTIVETo investigate diagnostic values of the detection of TMPRSS2-ERG gene fusion in metastatic prostate cancer.

METHODSA total of 32 fine needle aspiration (FNA) specimens of metastatic prostate carcinomas were retrieved from the pathology files at MD Anderson Cancer Center. The metastatic sites included the pelvic and remote lymph nodes, liver, bone, and thyroid gland. Immunohistochemical staining for PSA, PAP, synaptophysin, chromogranin A was performed. TMPRSS2-ERG gene fusion was evaluated on sections of cell blocks by fluorescence in situ hybridization (FISH) using ERG gene break-apart probes.

RESULTSThe mean age of the patients was 67 years. Twenty-six patients had a previous history of prostatic adenocarcinoma, while 6 patients presented initially with metastasis. In 11 patients, the metastatic lesions showed characteristic features of small cell carcinoma (SCC) and were positive for synaptophysin (9/9), chromogranin A (7/8), but negative for prostatic specific antigen (7/7). FISH analysis demonstrated a rearrangement of ERG gene in 10 of 32 cases (31.3%), and the rearrangement was associated with deletion of the 5' ERG gene in 6 cases. In addition, the copy number of ERG rearrangement gene locus was increased in 8 cases. Among the 11 cases with SCC features, a rearrangement of ERG gene was present in 5 cases, of which a deletion of the 5' ERG gene and increased copy number were seen in 3 cases.

CONCLUSIONSTMPRSS2-ERG gene fusion can be evaluated in FNA specimens of metastatic prostate cancer. Metastatic prostate cancers have a high prevalence of TMPRSS2-ERG gene fusion along with a frequent copy number increase of ERG gene. TMPRSS2-ERG gene fusion persists in metastatic prostate cancers and even in those with poorly differentiated SCC features. Therefore, an identification of the TMPRSS2-ERG gene fusion may be used to establish the prostatic origin of metastasis.

Acid Phosphatase ; Adenocarcinoma ; genetics ; metabolism ; pathology ; secondary ; surgery ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle ; Carcinoma, Small Cell ; genetics ; metabolism ; pathology ; secondary ; surgery ; Chromogranin A ; metabolism ; Follow-Up Studies ; Gene Fusion ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Liver Neoplasms ; genetics ; metabolism ; pathology ; secondary ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; genetics ; metabolism ; Prostate-Specific Antigen ; metabolism ; Prostatic Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Protein Tyrosine Phosphatases ; metabolism ; Synaptophysin ; metabolism

A cure cannot be assured for all men with clinically localized prostate cancer undergoing radical treatment. Molecular markers would be invaluable if they could improve the prediction of occult metastatic disease. This study was carried out to investigate the expression of BCL-2, Ki-67, p53 and E-cadherin in radical prostatectomy specimens. We sought to assess their ability to predict early biochemical relapse in a specific therapeutic setting. Eighty-two patients comprising 41 case pairs were matched for pathological stage, Gleason grade and preoperative prostate-specific antigen (PSA) concentration. One patient in each pair had biochemical recurrence (defined as PSA >or= 0.2 ng mL(-1) within 2 years of surgery) and the other remained biochemically free of disease (defined as undetectable PSA at least 3 years after surgery). Immunohistochemical analysis was performed to assess marker expression on four replicate tissue microarrays constructed with benign and malignant tissue from each radical prostatectomy specimen. Ki-67, p53 and BCL-2, but not E-cadherin, were significantly upregulated in prostate adenocarcinoma compared with benign prostate tissue (P < 0.01). However, no significant differences in expression of any of the markers were observed when comparing patients who developed early biochemical relapse with patients who had no biochemical recurrence. This study showed that expression of p53, BCL-2 and Ki-67 was upregulated in clinically localized prostate cancer compared with benign prostate tissue, with no alteration in E-cadherin expression. Biomarker upregulation had no prognostic value for biochemical recurrence after radical prostatectomy, even after considering pathological stage, whole tumour Gleason grade and preoperative serum PSA level.
Adenocarcinoma ; diagnosis ; metabolism ; surgery ; Aged ; Biomarkers, Tumor ; metabolism ; Cadherins ; genetics ; metabolism ; Case-Control Studies ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Ki-67 Antigen ; genetics ; metabolism ; Male ; Middle Aged ; Prognosis ; Prostate ; metabolism ; pathology ; Prostate-Specific Antigen ; blood ; Prostatectomy ; Prostatic Neoplasms ; diagnosis ; metabolism ; surgery ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Risk Factors ; Tumor Suppressor Protein p53 ; genetics ; metabolism

PURPOSE: Genetic variations among prostate cancer (PCa) patients who underwent radical prostatectomy (RP) and pelvic lymph node dissection were evaluated to predict lymph node invasion (LNI). Exome arrays were used to develop a clinicogenetic model that combined clinical data related to PCa and individual genetic variations. MATERIALS AND METHODS: We genotyped 242,186 single-nucleotide polymorphisms (SNPs) by using a custom HumanExome BeadChip v1.0 (Illumina Inc.) from the blood DNA of 341 patients with PCa. The genetic data were analyzed to calculate an odds ratio as an estimate of the relative risk of LNI. We compared the accuracies of the multivariate logistic model incorporating clinical factors between the included and excluded selected SNPs. The Cox proportional hazard models with or without genetic factors for predicting biochemical recurrence (BCR) were analyzed. RESULTS: The genetic analysis indicated that five SNPs (rs75444444, rs8055236, rs2301277, rs9300039, and rs6908581) were significant for predicting LNI in patients with PCa. When a multivariate model incorporating clinical factors was devised to predict LNI, the predictive accuracy of the multivariate model was 80.7%. By adding genetic factors in the aforementioned multivariate model, the predictive accuracy increased to 93.2% (p=0.006). These genetic variations were significant factors for predicting BCR after adjustment for other variables and after adding the predictive gain to BCR. CONCLUSIONS: Based on the results of the exome array, the selected SNPs were predictors for LNI. The addition of individualized genetic information effectively enhanced the predictive accuracy of LNI and BCR among patients with PCa who underwent RP.
Aged ; Biomarkers, Tumor/*genetics ; Biopsy ; DNA, Neoplasm/genetics ; Exome ; Gene Frequency ; Genome ; Genotype ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; *Models, Genetic ; Neoplasm Invasiveness ; Polymorphism, Single Nucleotide ; Predictive Value of Tests ; Prospective Studies ; Prostatectomy ; Prostatic Neoplasms/*genetics/pathology/surgery

OBJECTIVETo detect the expression of RhoC and Rho kinase 1 (ROCK-1) in prostate carcinoma, and explore the possible mechanism of RhoC/ROCK-1 in the pathogenesis of prostate carcinoma.

METHODSTissue specimens from 73 patients with prostate carcinoma and corresponding paracancerous tissues were obtained by prostate cancer biopsy or radical prostatectomy. The expression of RhoC/ROCK-1 mRNA was detected by RT-PCR. Western blot and immunohistochemistry were performed to dertect the expression of RhoC/ROCK-1 protein. Eukaryotic expression plasmids of RhoC were constructed and transfected into PC-3M-2B4 cells. p-MAPK and p-Akt were detected by Western bolt.

RESULTSThe expression levels of RhoC and ROCK-1 mRNA in the prostate carcinomas were significantly higher than those in corresponding paracancerous tissues [72.6% (53/73) vs. 34.2% (25/73); 68.5% (50/73) vs. 38.4% (28/73), P < 0.01], respectively. The results indicated that RhoC/ROCK-1 mRNA expression had no significant correlation with Gleason grade. However, the expression of RhoC/ROCK-1 mRNA showed a significant positive correlation with distant metastasis. The RhoC/ROCK-1 protein expression in prostate cancer was also higher than corresponding paracancerous tissues, and showed a significant positive correlation with p-MAPK and p-Akt expression levels. In addition, p-MAPK and p-Akt expression levels were up-regulated in the transcripts.

CONCLUSIONExpression levels of RhoC and ROCK-1 in prostate carcinoma are higher than those in corresponding paracancerous tissues, showing a significant positive correlation with distant metastasis. RhoC/ROCK-1 may be involved in the development, invasion and metastasis of prostate carcinoma.

Bone Neoplasms ; metabolism ; secondary ; Cell Line, Tumor ; Humans ; Male ; Mitogen-Activated Protein Kinases ; metabolism ; Neoplasm Grading ; Neoplasm Staging ; Phosphorylation ; Prostatectomy ; Prostatic Neoplasms ; metabolism ; pathology ; surgery ; Proto-Oncogene Proteins c-akt ; metabolism ; RNA, Messenger ; metabolism ; Transfection ; Up-Regulation ; rho GTP-Binding Proteins ; genetics ; metabolism ; rho-Associated Kinases ; genetics ; metabolism ; rhoC GTP-Binding Protein