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J L Mohler

Publications and source records attributed to J L Mohler.

At least 19 recordsLinked to original sources
PubMed2000

HE2beta and HE2gamma, new members of an epididymis-specific family of androgen-regulated proteins in the human.

HE2 is an epididymis-specific sperm-binding secretory protein. We isolated a family of HE2-related complementary DNAs from a human caput/corpus library. The transcripts code for identical 71-amino acid N-termini and different C-termini, and 5'- and 3'-untranslated regions. Compared with the original HE2, HE2beta and HE2gamma proteins have a 25-amino acid deletion near the C-terminus, and HE2gamma isoforms have a second deletion. These frame-shifting deletions result in C-termini differing in length, amino acid sequence, including number of cysteines, and isoelectric point. Identical sequences and deletion start and stop points indicate the HE2 isoforms are derived from alternative splicing of 8 or more exons of a single gene. Northern hybridization revealed that the 0.9-kb messenger RNA (mRNA) is most abundant in human caput; there is much less of it (20%) in corpus and little (<5%) in cauda. In castrated Macaca mulatta, HE2 mRNA decreased to 10% of sham-operated levels. Testosterone replacement maintained HE2 mRNA 3- to 5-fold higher than castrate levels, indicating its androgen dependence. Immunohistochemical staining revealed that the beta1 form is highly expressed in principal cells of the initial segment and caput. It is secreted into the lumen and binds to the sperm surface in the postacrosomal and neck regions. The beta2 form is expressed in principal cells primarily in efferent ducts.

3' Untranslated Regions↗
PubMed1999

Overexpression of cyclin D1 is rare in human prostate carcinoma.

BACKGROUND: Overexpression of cyclin D1 has been documented in a number of human cancers. Increased expression of cyclin D1 can contribute to cellular transformation and abnormal proliferation. METHODS: Quantitative RT-PCR and/or Western blot analysis were used to determine the level of cyclin D1 expression in 96 human prostate tumors, 15 benign prostate hyperplasias, 4 prostate cancer cell lines, and 3 xenografts. RESULTS: Our results demonstrate that 4.2% of the prostate tumors examined overexpressed cyclin D1 transcripts. In the cell lines, expression was normal, with the exception that reduced levels of cyclin D1 transcript and protein were observed in the DU145 cell line, as expected from cells with mutant RB. Normal levels of cyclin D1 were found in all xenograft tumors and BPH specimens examined. CONCLUSIONS: These data show that overexpression of cyclin D1 occurs rarely in human prostate tumors. However, when overexpression of cyclin D1 does occur, it may identify a subset of tumors with a different molecular biology.

Blotting, Southern↗
PubMed1999

Immunohistochemical quantitation of androgen receptor expression using color video image analysis.

BACKGROUND: The immunostaining features of the androgen receptor (AR) have been studied in prostate cancer (CaP) to predict the outcome of androgen deprivation therapies. We have developed an automatic video color image analysis system for quantitation of AR expression in large samples of prostatic nuclei. METHODS: Essential criteria of immunostaining have been examined to establish a linear relationship between AR protein content and mean optical density (MOD) of the immunoperoxidase-substrate reaction product. Titration of monoclonal AR antibody, F39.4.1, and concentration and reaction time of substrate were optimized using color video image analysis. The methodology was tested twice. First, CWR22 human CaP xenograft specimens, harvested from testosterone (T)-stimulated, castrated and T-resupplemented mice, were immunostained to demonstrate the dependence of AR expression on serum androgen levels. Second, AR expression was measured in archived clinical specimens. RESULTS: In CWR22 tumor-bearing mice castrated for 6 days, AR MOD decreased to 57% of T-stimulated, intact mice. After 72 hrs of T treatment, AR MOD returned to the level measured in T-stimulated, intact mice. Sixteen radical prostatectomy specimens and 16 transurethral resection of prostate (TURP) specimens were double-labeled with F39.4.1 and anti-cytokeratin MAb (13betaE12) specific for basal epithelial cells. Benign epithelial cells exhibited lower AR MOD in prostatectomy compared to TURP specimens (P < 0.01). Differences in AR immunostaining intensity may have resulted from differences in tissue fixation of whole organ versus small tissue specimens. CONCLUSIONS: AR immunostaining can be quantitated accurately using optimized immunohistochemical criteria and video image analysis.

Animals↗
PubMed1999

Prostate cancer risk and polymorphism in 17 hydroxylase (CYP17) and steroid reductase (SRD5A2).

Prostate cancer is the most common malignancy in males and is the second most common cause of cancer mortality in American men. Polymorphisms have been identified in two genes, the 17-hydroxylase cytochrome P450 gene (CYP17) and the steroid 5-reductase type II gene (SRD5A2) that are involved with androgen biosynthesis and metabolism. The CYP17 A2 allele contains a T-->C transition in the 5' promoter region that creates an additional Sp1-type (CCACC box) promoter site. The SRD5A2 valine to leucine (V89L) polymorphism has been correlated with lower dihydroxytestosterone levels. We tested genotypes in 108 prostate cases and 167 controls along with samples (n = 340) from several different ethnic groups. The CYP17 A2 allele (combined A1/A2 and A2/A2 genotypes) occurred at a higher frequency in Caucasian patients with prostate cancer (70%) than in Caucasian clinical control urology patients (57%), suggesting that the A2 allele may convey increased risk for prostate cancer [odds ratio (OR) = 1.7, 95% confidence interval (CI) = 1.0-3.0]. Blacks and Caucasians had a similar frequency of the A2 genotype (16 and 17%, respectively) while Taiwanese had the highest frequency (27%). The SRD5A2 leucine genotype was most frequent in Taiwanese (28%), intermediate in Caucasians (8.5%) and lowest in Blacks (2.5%). Genotypes having a SRD5A2 leucine allele were somewhat more common in prostate cancer cases (56%) than in controls (49%) (OR = 1.4, 95% CI = 0.8-2.2) but this difference was not significant. These results support the hypothesis that some allelic variants of genes involved in androgen biosynthesis and metabolism may be associated with prostate cancer risk.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1999

Androgen receptor up-regulates insulin-like growth factor binding protein-5 (IGFBP-5) expression in a human prostate cancer xenograft.

The insulin-like growth factor (IGF) binding proteins (IGFBPs) are important modulators of IGF action in many tissues including human prostate. IGFBPs and the androgen receptor (AR) are expressed in CWR22, an androgen-dependent epithelial cell human CaP xenograft that retains biological characteristics of human CaPs, including regression following androgen withdrawal and recurrent growth of AR-containing cells in the absence of testicular androgens beginning several months after castration. Northern blot and in situ hybridization analyses demonstrated that IGFBP-5 is androgen-regulated in CWR22. IGFBP-5 messenger RNA (mRNA) decreased by 90% following castration of tumor-bearing mice compared with noncastrate androgen-stimulated mice. Testosterone treatment of CWR22 tumor-bearing mice 6 or 12 days after castration increased IGFBP-5 mRNA 10- to 12-fold. Levels of other IGFBP mRNAs did not change following androgen withdrawal and replacement. IGFBP-5 protein in tumor extracts bound 125I-labeled IGF-I in ligand blot assays and the amounts of IGFBP-5 measured by immunoblotting paralleled the levels of IGFBP-5 mRNA. Androgen-induced expression of IGFBP-5 was at a maximum level within 24 h after testosterone replacement, whereas the major increase in cell proliferation as measured by Ki-67 immunostaining occurred between 24-48 h. This time course suggested IGFBP-5 may be a mediator of androgen-induced growth of CWR22. In tumors that recurred several months following castration, IGFBP-5 mRNA and protein increased to levels that approached those in androgen-stimulated CWR22 tumors from noncastrate mice. IGFBP-5 immunohistochemical staining of prostate tissue specimens from patients was stronger in androgen-dependent and androgen-independent CaP than in areas of intraepithelial neoplasia (PIN) or benign prostatic hyperplasia (BPH). IGFBP-5 mRNA in these specimens was localized predominantly to stromal cells and IGFBP-5 protein to epithelial cell membranes.

Animals↗
PubMed1998

Androgen receptor expression in androgen-independent prostate cancer is associated with increased expression of androgen-regulated genes.

The human prostate cancer (CaP) xenograft, CWR22, mimics human CaP. CWR22 grows in testosterone-stimulated nude mice, regresses after castration, and recurs after 5-6 months in the absence of testicular androgen. Like human CaP that recurs during androgen deprivation therapy, the recurrent CWR22 expresses high levels of androgen receptor (AR). Immunohistochemical, Western, and Northern blot analyses demonstrated that AR expression in the androgen-independent CWR22 is similar to AR expression in the androgen-dependent CWR22 prior to castration. Expression of prostate-specific antigen and human kallikrein-2 mRNAs, two well-characterized androgen-regulated genes in human CaP, was androgen dependent in CWR22. Despite the absence of testicular androgen, prostate-specific antigen and human kallikrein-2 mRNA levels in recurrent CWR22 were higher than the levels in regressing CWR22 tumors from 12-day castrate mice and similar to those in the androgen-stimulated CWR22. Other AR-regulated genes followed a similar pattern of expression. Differential expression screening identified androgen regulation of alpha-enolase and alpha-tubulin as well as other unknown mRNAs. Insulin-like growth factor binding protein-5, the homeobox gene Nkx 3.1, the AR coactivator ARA-70, and cell cycle genes Cdk1 and Cdk2 were androgen regulated in CWR22. In recurrent CWR22, the steady-state levels of all these AR-dependent mRNAs were similar to those in the androgen-stimulated CWR22, despite the absence of testicular androgen. Expression of AR and AR-regulated genes in the androgen-deprived recurrent CWR22 at levels similar to the androgen-stimulated CWR22 suggests that AR is transcriptionally active in recurrent CWR22. Induction of these AR-regulated genes may enhance cellular proliferation in relative androgen absence but through an AR-dependent mechanism. Alternatively, in androgen-independent tumors, induced expression of the AR-regulated gene network might result from a non-AR transcription control mechanism common to these genes.

Animals↗
PubMed1998

The role of N-acetylation polymorphisms in smoking-associated bladder cancer: evidence of a gene-gene-exposure three-way interaction.

Arylamines are known bladder carcinogens and are an important constituent of tobacco smoke. The handling of arylamines in the body is complex and includes metabolism by NAT1 and NAT2, enzymes that play a role in both activation and detoxification of arylamines and their congeners. Both NAT1 and NAT2 are polymorphic, with alleles that have been shown to correlate with higher or lower enzyme activity. To explore the combined role of these genes and exposure on bladder cancer risk, we examined the NAT1 and NAT2 genotype in a case-control study of bladder cancer in which detailed exposure histories were available on all 230 cases and 203 frequency-matched controls. Using PCR-RFLP genotyping, we determined NAT2 genotype for the five most common alleles, NAT2*4, NAT2*5, NAT2*6, NAT2*7, NAT2*14 (frequently referred to as WT, M1, M2, M3, and M4, respectively). Similarly, the NAT1 genotype was determined for the four most common alleles NAT1*3, NAT1*4, and NAT1*11, and the putative high-activity allele, NAT1*10. No association between NAT2 genotype and bladder cancer risk was found whether genotype was considered alone or in combination with smoking, in either stratified or logistic regression analysis that adjusted for age, sex, and race. Stratified and logistic regression analysis both demonstrated an increased risk for individuals carrying the NAT1*10 allele among smokers. There was evidence of a gene-dosage effect, such that those who were homozygous for the NAT1*10 allele had the highest risks. There was also evidence of a statistically significant gene-environment interaction, such that bladder cancer risk depends on both NAT1 genotype and smoking exposure. Interestingly, although NAT2 genotype did not influence risk either alone or in combination with smoking exposure, there was evidence of a statistically significant gene-gene-environment three-way interaction. Bladder cancer risk from smoking exposure is particularly high in those who inherit NAT2 slow alleles in combination with one or two copies of the NAT1*10 allele. A biological mechanism for this finding is suggested.

Acetylation↗
PubMed1998

Downregulation of the beta4 integrin subunit in prostatic carcinoma and prostatic intraepithelial neoplasia.

Integrins are adhesion receptors thought to be important in the process of cancer cell invasion and metastasis. Unlike other integrins, which attach a cell to extracellular matrix molecules, the alpha6beta4 integrin participates in the formation of hemidesmosomes, attaching epithelial cells to the basement membrane. Investigations of the alpha6beta4 integrin in human prostatic carcinoma have yielded conflicting results and have been primarily qualitative rather than quantitative. Expression of the beta4 integrin subunit was determined using rat monoclonal antibody 439-9B and image analysis in regions of benign prostatic epithelium (BPE), high-grade prostatic intraepithelial neoplasia (PIN), and prostatic carcinoma (CaP) in 38 patients treated by radical prostatectomy for clinically localized CaP. The beta4 integrin subunit was significantly downregulated in CaP compared with BPE; PIN stained intermediate in intensity between BPE and CaP. Thirty-four of 35 patients showed downregulation of the beta4 integrin subunit, and all 15 patients with PIN had downregulation of beta4 in PIN as compared with BPE. Degree of downregulation of the beta4 integrin subunit did not add prognostic significance to the information present at initial biopsy (age, clinical stage, clinical grade, and serum prostate-specific antigen level). There was no correlation between intensity of staining of CaP, absolute change in staining, or percent loss of beta4 integrin subunit staining with age, pathological stage, or Gleason's score. Downregulation of the beta4 integrin in CaP and PIN compared with BPE may be correlated with neoplastic transformation of the prostate and loss of hemidesmosomes or basal epithelial cells.

Aged↗
PubMed1998

Patient positioning for radical retropubic prostatectomy.

Proper positioning of a surgical patient reduces morbidity and mortality. We describe a method of patient positioning involving elevation of the lower extremities and protection of the brachial plexus that reduces complication rates in radical retropubic prostatectomy.

Aged↗
PubMed1998

Isolation and characterization of propagable cell lines (HUNC) from the androgen-sensitive Dunning R3327H rat prostatic adenocarcinoma.

The Dunning H rat prostate tumor (R3327H) is a widely used experimental model of human prostatic adenocarcinoma (CaP). The Dunning H tumor has been characterized as androgen-sensitive, androgen-receptor (AR) positive, prostate-specific antigen and prostatic acid phosphatase (PAP) positive. To date, the tumor has been maintained by serial passage in vivo because of the lack of an in vitro cell line that retains the characteristics of the in vivo tumor. The objective of the present study was to establish a propagable cell line from R3327H adenocarcinoma that maintained androgen sensitivity and expression of AR, PSA and PAP. Tissue harvested from an in vivo R3327H tumor was dissociated with collagenase and placed into Richter's improved media (with supplements). A cytokeratin-positive epithelial cell line (HUNC-E) and a vimentin-positive stromal cell line (HUNC-S) were generated from the primary culture, subcultured continuously for >300 days, and passaged >50 times. Survival of the HUNC-E cell line in vitro depended on several media supplements, including nicotinamide, insulin, transferrin, selenium and epidermal growth factor (EGF). HUNC-E cells expressed AR and produced PSA and PAP throughout the culture period, as confirmed by immunocytochemistry and Western blot analyses. Addition of 14 nM testosterone (T) or dihydrotestosterone (DHT) to HUNC-E cells, stimulated DNA synthesis as well as anchorage-independent growth and PSA production, which demonstrated the androgen-sensitive nature of the cells in vitro. When HUNC-E and HUNC-S cells were combined in a 3:1 ratio and introduced subcutaneously into syngeneic male hosts, tumors formed in 2/3 animals with an average latency of 7 months. RT-PCR and immunocytochemical characterization of the HUNC cell lines revealed that the cells expressed several growth factors and their cognate receptors, including HGF, TGF-alpha and the TGF-betas, indicating the establishment of potential autocrine loops in the neoplastic cells. The HUNC-E and HUNC-S CaP cell lines, which retain the characteristics of the epithelial and stromal components of the in vivo R3327H tumor, will allow a more thorough and informative molecular and biological analysis of prostatic adenocarcinoma.

Acid Phosphatase↗
PubMed1997

Expectant management as an option for men with stage T1c prostate cancer: a preliminary study.

The outcome of patients selecting observation of clinical stage T1c prostate cancer is unknown. A total of 101 men with clinical stage T1c prostate cancer were evaluated, counseled, and monitored in a standard fashion. Altogether, 27 men who elected observation were older and had greater co-morbidity but similar tumor characteristics as compared with 74 men who elected radical prostatectomy. In all, 9 men demonstrated clinical or biochemical evidence of progression after a mean follow-up of 23 months; 4 men who underwent radical prostatectomy had specimen-confined disease and undetectable post-operative levels of PSA. Observation appears to be a viable option for some men with clinical stage T1c prostate cancer.

Aged↗
PubMed1997

In situ hybridization studies of metalloproteinases 2 and 9 and TIMP-1 and TIMP-2 expression in human prostate cancer.

The expression of MMP-2, MMP-9, TIMP-1, TIMP-2, and the urokinase receptor were examined in fetal and normal prostate tissues, benign prostatic hyperplasia and prostate cancer (n = 117). In situ hybridization with digoxigenin-labeled oligonucleotide probes demonstrated that TIMP-1 and TIMP-2 were expressed at elevated levels in the stroma of Gleason sum 5 tissues, whereas MMP-2 and MMP-9 were expressed at relatively low levels. In higher Gleason sum tissues (GS 8-10), TIMP-1 and TIMP-2 were not expressed, whereas MMP-2 and MMP-9 were intensely expressed. Furthermore, TIMP-1 and TIMP-2 expression was high in organ-confined specimens (OC, n = 43), somewhat lower in specimens with capsular penetration (CP, n = 29), and low or negative in samples with surgical margin/seminal vesicle (M/SV, n = 17) and lymph node (LN, n = 13) involvement. In contrast, MMP-2 and MMP-9 expression was low in the OC tissues; and noticeably higher in CP, M/SV, and LN specimens. Finally, correlation of TIMP and MMP expression with GS and pathological stage versus cure rate further revealed that a high percentage of organ-confined, GS 5 specimens expressing TIMP and little MMP were cured. In comparison, few of the GS 7-10 patients with capsular penetration and expressing MMP and little TIMP were cured. The data suggest that TIMP-1 (and TIMP-2) and MMP-2 (and MMP-9) are independent predictors of outcome.

Collagenases↗
PubMed1997

Dehydroepiandrosterone activates mutant androgen receptors expressed in the androgen-dependent human prostate cancer xenograft CWR22 and LNCaP cells.

An androgen receptor (AR) gene mutation identified in the androgen-dependent human prostate cancer xenograft, CWR22, changed codon 874 in the ligand-binding domain (exon H) from CAT for histidine to TAT for tyrosine and abolished a restriction site for the endonuclease SfaNI. SfaNI digestion of AR exon H DNA from normal but not from prostate cancer tissue indicated H874Y is a somatic mutation that occurred before the initial tumor transplant. CWR22, an epithelial cell tumor, expresses a 9.6-kb AR mRNA similar in size to the AR mRNA in human benign prostatic hyperplasia. AR protein is present in cell nuclei by immunostaining as in other androgen-responsive tissues. Transcriptional activity of recombinant H874Y transiently expressed in CV1 cells in the presence of testosterone or dihydrotestosterone was similar to that of wild type AR. With dihydrotestosterone at a near physiological concentration (0.01 nM), H874Y and wild type AR induced 2-fold greater luciferase activity than did the LNCaP mutant AR T877A. The adrenal androgen, dehydroepiandrosterone (10 and 100 nM) with H874Y stimulated a 3- to 8-fold greater response than with wild type AR and at 100 nM the response was similar with the LNCaP mutant. H874Y, like the LNCaP cell mutant, was more responsive to estradiol and progesterone than was wild type AR. The antiandrogen hydroxyflutamide (10 nM) had greater agonist activity (4- to 7-fold) with both mutant ARs than with wild type AR. AR mutations that alter ligand specificity may influence tumor progression subsequent to androgen withdrawal by making the AR more responsive to adrenal androgens or antiandrogens.

Androgen Antagonists↗
PubMed1996

Association of prostate cancer with vitamin D receptor gene polymorphism.

The incidence of prostate cancer in the United States is second only to skin cancers, and the disease kills almost the same number of men as breast cancer does women. Relatively few risk factors are known for prostate cancer, although several lines of evidence suggest that vitamin D may be an important determinant of prostate cancer risk. A series of common polymorphisms in the vitamin D receptor gene were recently reported to be associated with bone density and risk of osteoporosis (Morrison et al., Nature (Lond.), 367: 284-287, 1994). These genetic variants have been correlated with both circulating levels of active vitamin D hormone and in vitro measures of gene expression (Morrison et al., Nature (Lond.), 367: 284-287, 1994). We tested the hypothesis that vitamin D receptor gene polymorphisms are associated with prostate cancer risk using a case-control study of 108 men undergoing radical prostatectomy and 170 male urology clinic controls with no history of cancer. Among the white control group, 22% were homozygous for the presence of a TaqI RFLP at codon 352 (genotype tt), but only 8% of cases had this genotype (P < 0.01). A similar trend was seen among the small number of blacks in this study (13% for controls, 8% for cases), although the difference was not statistically significant. Race-adjusted combined analysis suggests that men who are homozygous for the t allele (shown to correlate with higher serum levels of the active form of vitamin D) have one-third the risk of developing prostate cancer requiring prostatectomy compared to men who are heterozygotes or homozygous for the T allele (odds ratioMH = 0.34; 95% confidence interval, 0.16-0.76; P < 0.01). These results support recent ecological, population, and in vitro studies suggesting that vitamin D is an important determinant of prostate cancer risk and, if confirmed, suggest strategies for chemoprevention of this common cancer.

Black or African American↗
PubMed1996

The role of motility proteins and metastasis-suppressor genes in prostate cancer progression.

In 1996, an estimated 317,000 new cases of prostate cancer will be diagnosed in the United States. The incidence of prostate cancer has more than doubled in the past five years; in fact, it is estimated that aggressive screening starting at age 50 could potentially identify 10,000,000 American men with histologically localized prostate cancer. In order to reduce deaths from prostate cancer, it is necessary not only to diagnose but also to accurately predict the clinical course of an individual patient's cancer, thus allowing for more effectively directed treatment. Acquisition of metastatic ability is a well-recognized criterion for the aggressiveness of prostate cancer. A number of molecular and cellular changes associated with the malignant progression of prostate cancer have been identified. Certain of these changes may potentially be used as markers for metastatic ability of histologically localized prostate cancer cells. This concise review will consider two parameters which are associated with the acquisition of metastatic ability: increased cellular motility and loss of metastasis-suppressor gene function. A link between these two parameters has been demonstrated and may contribute to the development of innovative approaches for predicting the metastatic ability of individual tumors.

Cell Movement↗
PubMed1996

Comparison of subcapsular and total orchiectomy for treatment of metastatic prostate cancer.

OBJECTIVES: To determine whether subcapsular orchiectomy provides suboptimal treatment of metastatic prostate cancer when used to avoid the psychologic consequences of the empty scrotum that results from total orchiectomy. METHODS: We compared testosterone and prostate-specific antigen levels and survival of 37 patients who underwent total orchiectomy and 37 patients who underwent subcapsular orchiectomy for metastatic prostate cancer. RESULTS: The two groups of 37 patients were similar by clinical parameters. Postoperatively, testosterone levels were 21 +/- 11 ng/dL for subcapsular versus 21 +/- 9 ng/dL for total orchiectomy patients. Tumor response was similar in the two groups when assessed by prostate-specific antigen measured 3 weeks, 6 months, and 1, 2, and 3 years postoperatively. Survival was similar when assessed using Kaplan-Meier analysis (P = 0.76). CONCLUSIONS: Subcapsular orchiectomy is a viable option for treatment of metastatic prostate cancer.

Aged↗
PubMed1996

Cathepsin D and epidermal growth factor receptor immunohistochemistry does not predict recurrence of prostate cancer in patients undergoing radical prostatectomy.

PURPOSE: We determined if immunohistochemical expression of the epidermal growth factor receptor and cathepsin D in the primary tumor was of prognostic value in clinically localized prostate cancer after radical prostatectomy. MATERIALS AND METHODS: Immunohistochemical staining for epidermal growth factor receptor and cathepsin D was performed on 105 radical prostatectomy specimens from 2 academic centers. The epidermal growth factor receptor and cathepsin D expressions were graded using H scoring by an experienced pathologist blinded to other patient data, and compared with age, grade, stage, race and initial serologic (prostate specific antigen) recurrence. Univariate and multivariate statistical testing was performed. RESULTS: Immunohistochemically detectable epidermal growth factor receptor and cathepsin D expression was not correlated to age, race, stage or Gleason grade. In univariate and multivariate testing epidermal growth factor receptor and cathepsin D were not prognostic markers for disease progression following radical prostatectomy. CONCLUSIONS: Immunohistochemical analysis of the biomarkers cathepsin D and epidermal growth factor receptor in radical prostatectomy specimens does not predict disease recurrence. Further biological marker study is needed in clinically localized prostate cancer.

Aged↗