Occurrence of paratesticular ganglioneuroma 18 years after concurrent adrenal ganglioneuroma and papillary thyroid carcinoma - a case report.

BACKGROUND: Ganglioneuromas (GNs) are composed of mature ganglion cells and Schwann cells with a fibrous stroma; GNs are most often observed in children and young adults. The majority of non-cranial GNs are located in the retroperitoneum and posterior mediastinum. Other reported rare sites include the adrenal gland, small intestine, colon and urinary bladder. However, para-testicular GNs are even more rare. CASE PRESENTATION: Herein, we report the case of a patient with concurrent adrenal GN and thyroid papillary carcinoma who developed paratesticular GN eighteen years later. CONCLUSIONS: We conclude that there is an association among papillary thyroid carcinoma, GN and MEN2 syndromes. This case report may provide important information for the proposed association. However, further studies are required.

Co-modulated behavior and effects of differentially expressed miRNA in colorectal cancer.

BACKGROUND: MicroRNAs (miRNAs) are short noncoding RNAs (approximately 22 nucleotides in length) that play important roles in colorectal cancer (CRC) progression through silencing gene expression. Numerous dysregulated miRNAs simultaneously participate in the process of colon cancer development. However, the detailed mechanisms and biological functions of co-expressed miRNA in colorectal carcinogenesis have yet to be fully elucidated. RESULTS: The objective of this study was to identify the dysfunctional miRNAs and their target mRNAs using a wet-lab experimental and dry-lab bioinformatics approach. The differentially expressed miRNA candidates were identified from 2 miRNA profiles, and were confirmed in CRC clinical samples using reported target genes of dysfunctional miRNAs to perform functional pathway enrichment analysis. Potential target gene candidates were predicted by an in silico search, and their expression levels between normal and colorectal tumor tissues were further analyzed using real-time polymerase chain reaction (RT-PCR). CONCLUSION: Fifteen dysfunctional miRNAs were engaged in metastasis-associated pathways through comodulating 7 target genes, which were identified by using a multi-step approach. The roles of these candidate genes are worth further exploration in the progression of colon cancer, and could potentially be targets in future therapy.

WWOX protein expression varies among RCC histotypes and downregulation of WWOX protein correlates with less-favorable prognosis in clear RCC.

BACKGROUND: WWOX has been shown to be a candidate tumor suppressor gene in numerous human cancers. The objective of this study is to determine the expression of WWOX in human renal cell carcinoma tumor cells and its possible correlation with clinical outcome. METHODS: The WWOX protein expressions of human renal cell carcinoma (RCC) tumor and of matched normal renal parenchyma were examined, and its correlation with clinical cancer-specific survival was investigated. RESULTS: Downregulation of WWOX only in clear cell type RCC was demonstrated in our results including immunohistochemistry, Western blot, and RT-PCR assay. For the remnant cell types of RCC, sample sizes were insufficient to draw any conclusion of WWOX protein expression. The decreased expression of WWOX in clear cell RCC tumor compared with matched normal renal parenchyma was also correlated with clinical cancer-specific survival (Kaplan-Meier, p=0.0482). CONCLUSIONS: We proved that the expression level of WWOX is downregulated in human clear cell RCC. Moreover, the decreased expression of WWOX in clear cell RCC tumor compared with matched normal renal parenchyma was also correlated with clinical cancer-specific survival. Since clear cell RCC is a special human cancer using unique molecular pathogenesis, further investigation will provide more linking intracellular signaling of WWOX and novel therapeutic targets of human renal cell carcinoma.

Prognostic significance of cyclin D1 polymorphisms on prostate-specific antigen recurrence after radical prostatectomy.

BACKGROUND: Cyclin D1 (CCND1) is an important cell-cycle regulator involved in carcinogenesis and progression of prostate cancer. We tested whether genetic variations within the CCND1 gene are related to clinical outcomes in prostate cancer patients receiving radical prostatectomy. METHODS: A total of 320 clinical localized prostate cancer patients who underwent radical prostatectomy in Taiwan were prospectively follow-up in this study. A total of 5 tagged single-nucleotide polymorphisms that captured the genetic variability across the CCND1 gene were genotyped, and the prognostic significance on prostate-specific antigen (PSA) recurrence was assessed using the Kaplan-Meier analysis and Cox regression model. RESULTS: We found a polymorphism, rs9344, and 2 haplotypes, GAGG and CTGG, consisting of rs667515, rs2450254, rs9344, and rs678653, were associated with PSA recurrence (P ≤ 0.033). After adjusting for other clinicopathologic predictors, including age, PSA levels, pathologic stage, Gleason score, and surgical margin, rs9344 and the haplotype CTGG remained significant (P ≤ 0.044). The model based on clinical variables plus CCND1 rs9344 or haplotype showed improvement over the model without genetic information, as indicated by ≥ 7.2 % net reclassification improvement (P ≤ 0.040), integrated discrimination index (P ≤ 0.041), and likelihood ratio test (P ≤ 0.028). CONCLUSION: Our data suggest that the CCND1 rs9344 and a specific haplotype CTGG may be prognostic factors for PSA recurrence after radical prostatectomy.

Significant associations of prostate-specific antigen nadir and time to prostate-specific antigen nadir with survival in prostate cancer patients treated with androgen-deprivation therapy.

OBJECTIVE: The influence of prostate-specific antigen (PSA) kinetics on the outcome of metastatic prostate cancer (PCa) after androgen-deprivation therapy (ADT) remains poorly characterised. We evaluated the prognostic significance of PSA nadir and time to PSA nadir as well as their interactive effect on prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT. METHODS: A total of 650 men with advanced or metastatic PCa treated with ADT were studied. The prognostic significance of PSA nadir and time to PSA nadir on PCSM and ACM were analysed using Kaplan-Meier analysis and the Cox regression model. RESULTS: On multivariate analysis, clinical M1 stage, Gleason Score 8-10, PSA nadir ≥ 0.2 ng/ml and time to PSA nadir < 10 months were independent predictors of PCSM and ACM. The combined analysis showed that patient with higher PSA nadir and shorter time to PSA nadir had significantly higher risk of PCSM and ACM compared to those with lower PSA nadir and longer time to PSA nadir (hazard ratios = 6.30 and 4.79, respectively, all P < 0.001). CONCLUSIONS: Our results suggest that higher PSA nadir level and faster time to reach PSA nadir after ADT were associated with shorter survival for PCa.

Non-inferiority of silodosin to tamsulosin in treating patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).

UNLABELLED: What's known on the subject? and What does the study add? Silodosin administered by 4 mg twice daily is as effective as tamsulosin 0.2 mg daily in treating patients with LUTS associated with BPH. Relative to tamsulosin, silodosin has less cardiovascular side effects as judged by the minimal changes of blood pressure and pulse rats after treatment. OBJECTIVE: • To test the hypothesis that the efficacy of silodosin would not be inferior to tamsulosin in treating patients with lower urinary tract symptoms associated with benign prostate hyperplasia (BPH). PATIENTS AND METHODS: • At nine medical centres, 209 patients with an International Prostate Symptom Score (IPSS) of ≥13 were randomized to silodosin (4 mg twice daily) or tamsulosin (0.2 mg once daily) for 12 weeks. • The primary efficacy measure was the mean change from baseline to endpoint in IPSS. • The non-inferiority margin of the IPSS change was set at 1.0. • Secondary efficacy measures included change in maximal urinary flow rate (Q(max)) and health-related quality of life (HRQL) score. RESULTS: • Of the 170 (81.3%) patients who completed the study, 86.2% in the silodosin group vs 81.9% in the tamsulosin group achieved a ≥25% decrease in IPSS (P= 0.53). • The mean difference (silodosin minus tamsulosin) in IPSS change from baseline was -0.60 (95% confidence interval -2.15, 0.95), inferring the non-inferiority of silodosin to tamsulosin. • The mean changes in the Q(max) and HRQL score from baseline were comparable between the groups (both, P > 0.05). Although patients receiving silodosin had a significantly higher incidence of abnormal ejaculation (9.7% vs tamsulosin 1.0%, P= 0.009), only 1.9% discontinued treatment. • Tamsulosin treatment resulted in a significant reduction in mean systolic blood pressure (-4.2 mmHg, within-group P= 0.004) relative to the negligible change of silodosin (-0.1 mmHg, within-group P= 0.96) CONCLUSION: • The trial shows the non-inferiority of silodosin 4 mg twice daily to tamsulosin 0.2 mg once daily in patients with symptoms of BPH.

Mixed epithelial and stromal tumor of the kidney with elevated serum level of cancer antigen 125.

Mixed epithelial and stromal tumor of the kidney is a newly categorized lesion, with few reported cases. We report a rare case of a 45-year-old woman with a palpable abdominal mass and elevated serum level of serum cancer antigen 125, who was not receiving hormones or contraceptive agents. Abdominal magnetic resonance imaging revealed a large multilocular cystic tumor that arose in the left central kidney. Nephrectomy was performed under the initial impression of cystic renal cell carcinoma; however, a diagnosis of mixed epithelial and stromal tumor was confirmed according to pathological and immunohistochemical findings. Serum level of cancer antigen 125 returned to normal after 1 month postoperatively and no recurrence was found in the following 18 months.

Clinical outcome of Taiwanese men with clinically localized prostate cancer post-radical prostatectomy: a comparison with other ethnic groups.

BACKGROUND: Prostate cancer incidence varies significantly among different ethnic groups. However, the report concerning the clinical outcome after radical prostatectomy (RP) in the low incidence Asian population is still limited. We aimed to compare the clinical outcome in patient treated with RP among different ethnic groups and to identify significant prognostic factors in Taiwanese patients. METHODS: A total of 341 patients with clinical localized prostate cancer undergoing curative RP in three medical centers in Taiwan were included in this study. Ethnic group comparison was performed using the CaPSURE, SEARCH databases from United States (US) and one large European series. The Kaplan-Meier analysis and Cox proportional hazard model were used to identify significant predictors for prostate-specific antigen (PSA) recurrence. RESULTS: Compared to the Caucasian white population in the US and Europe studies, the Taiwanese population have higher age at surgery and higher pre-operative PSA level. With mean and median follow-up of 39.1 months and 31.0 months (range 5-120 months), 127 men (37.2%) had PSA recurrence which was significant higher than the Western series. Significant predictors for PSA recurrence identified in the post-operative overall model were PSA level, pathological Gleason Score, pathological tumor stage and lymph node metastasis. CONCLUSIONS: The clinical outcome of Taiwanese male with prostate cancer post-RP appears inferior to the Western country, which is largely due to delay surgery at higher PSA level. Earlier diagnosis and treatment may improve the cancer control of RP.

Cadmium burden and the risk and phenotype of prostate cancer.

BACKGROUND: Studies on the association between prostate cancer and cadmium exposure have yielded conflicting results. This study explored cadmium burden on the risk and phenotype of prostate cancer in men with no evident environmental exposure. METHODS: Hospital-based 261 prostate cancer cases and 267 controls with benign diseases were recruited from four hospitals in Taiwan. Demographic, dietary and lifestyle data were collected by standardized questionnaires. Blood cadmium (BCd) and creatinine-adjusted urine cadmium (CAUCd) levels were measured for each participant. Statistical analyses measured the prostate cancer risk associated with BCd and CAUCd separately, controlling for age, smoking and institution. BCd and CAUCd levels within cases were compared in relation to the disease stage and the Gleason score. RESULTS: High family income, low beef intake, low dairy product consumption and positive family history were independently associated with the prostate carcinogenesis. There was no difference in BCd levels between cases and controls (median, 0.88 versus 0.87 microg/l, p = 0.45). Cases had lower CAUCd levels than controls (median, 0.94 versus 1.40 microg/g creatinine, p = 0.001). However, cases with higher BCd and CAUCd levels tended to be at more advanced stages and to have higher Gleason scores. The prostate cancer cases with Gleason scores of > or = 8 had an odds ratio of 2.89 (95% confidence interval 1.25-6.70), compared with patients with scores of 2-6. CONCLUSION: Higher CAUCd and BCd levels may be associated with advanced cancer phenotypes, but there was only a tenuous association between cadmium and prostate cancer.

Risk factors for individual domains of female sexual function.

INTRODUCTION: Female sexual function contains four major subtypes of desire, arousal, orgasm, and pain. Few studies used validated instruments to determine the dysfunction in these areas and assess their risk factors. AIM: To assess the prevalence of and risk factors for individual components of sexual difficulty in women. METHODS: A self-administered questionnaire containing the Female Sexual Function Index (FSFI) was given to 2,159 woman employees of two hospitals to assess their sexual function and its correlates. MAIN OUTCOME MEASURES: The associations between female sexual difficulty in individual domains defined by the FSFI domain scores and potential risk factors assessed by simple questions. RESULTS: Among the 1,580 respondents, 930 women's data were eligible for analysis with a mean age of 36.1 years (range 20-67). Of them, 43.8% had sexual difficulty in one or more domains, including low desire in 31.3%; low arousal, 18.2%; low lubrication, 4.8%; low orgasmic function, 10.4%; low satisfaction, 7.3%; and sexual pain, 10.5%. Compared with the younger women (20-49 years), the oldest age group (50-67 years) had a significantly higher prevalence in low desire, low arousal, and low lubrication, but not in the other domains. Based on multivariate logistic regression analyses, poor relationship with the partner and perception of partner's sexual dysfunction were major risk factors for low desire, low arousal, low orgasmic function, and low satisfaction. Age and urge urinary incontinence were associated with low lubrication and sexual pain. Most comorbidities were not related to these difficulties, except diabetes being related to low desire. CONCLUSIONS: Relationship factors had substantial impact on female sexual function in desire, arousal, orgasm, and satisfaction. On the other hand, women's lubrication problem and sexual pain were related predominantly with biological factors. These are initial results and future research is needed to confirm them.

Influence of cytokine gene polymorphisms on prostate-specific antigen recurrence in prostate cancer after radical prostatectomy.

PURPOSE: Evidence is accumulating indicating that chronic inflammation plays an important role in prostate cancer. We investigated the potential prognostic roles of IL-6, IL-8 and IL-10 polymorphisms in clinical localized prostate cancer after radical prostatectomy. MATERIALS AND METHODS: A total of 116 clinically localized prostate cancer patients undergoing curative radical prostatectomy were included in this study. The IL-6, IL-8 and IL-10 polymorphisms were determined by the TaqMan real-time PCR method. Their prognostic significance on prostate-specific antigen (PSA) recurrence was assessed using Kaplan-Meier analysis and Cox regression model. RESULTS: The IL-6 polymorphism (rs2066992) T/G and G/G genotype cases were associated with a higher percentage of preoperative PSA levels of > or =10 ng/ml; higher risk of positive surgical margin, and higher risk of extraprostatic extension compared to the T/T genotype. The IL-10 polymorphism (rs1800871) A/A genotype was associated with a higher risk of PSA recurrence compared with the A/G + G/G genotypes and significantly poorer PSA-free survival (log-rank test, p = 0.019). After considering other covariates in a Cox proportional hazard model, the IL-10A/A genotype and high Gleason score (8-10) were still independent predictors of poor PSA-free survival. CONCLUSION: Our results suggest that the IL-10 polymorphism may be a prognostic factor for PSA recurrence after radical prostatectomy.

Prognostic significance of p53 and X-ray repair cross-complementing group 1 polymorphisms on prostate-specific antigen recurrence in prostate cancer post radical prostatectomy.

PURPOSE: The tumor suppressor p53 and DNA repair gene X-ray repair cross-complementing group 1 (XRCC1) are thought to play important roles on prostate cancer susceptibility and tumor development. We investigated the potential prognostic roles of p53 (codon 72) and XRCC1 (codons 194, 280, and 399) polymorphisms in clinical localized prostate cancer after radical prostatectomy. EXPERIMENTAL DESIGN: A total of 126 clinical localized prostate cancer patients undergoing curative radical prostatectomy at the Kaohsiung Medical University Hospital and Kaohsiung Veterans General Hospital were included in this study. The p53 codon 72 and XRCC1 codons 194, 280 and 399 polymorphisms were determined by the PCR-RFLP method. Their prognostic significance on prostate-specific antigen (PSA) recurrence were assessed using the Kaplan-Meier analysis and Cox regression model. RESULTS: The p53 codon 72 Arg/Arg genotype was associated with increased PSA recurrence risk compared with the Arg/Pro and Pro/Pro genotypes, although the difference did not reach significance (30.3% versus 20.4%, P = 0.247). Of these three XRCC1 polymorphisms, the codon 399 Arg/Gln + Gln/Gn genotypes were significantly associated with higher risk of PSA recurrence after radical prostatectomy compared with the Arg/Arg genotype (34.0% versus 15.1%, P = 0.013) and poorer PSA-free survival (log-rank test, P = 0.0056). After considering for other covariates in a Cox proportional hazard model, the XRCC1 Arg/Gln and Gln/Gln genotypes (hazard ratio, 4.73; 95% confidence interval, 1.61-13.92; P = 0.005) and high Gleason score (Gleason score, 8-10; hazard ratio, 5.58; 95% confidence interval, 1.58-19.71; P = 0.008) were still independent predictors of poor PSA-free survival after radical prostatectomy. The similar significant results were not found in XRCC1 codons 194 and 280. CONCLUSIONS: Our results suggest that the XRCC1 codon 399 polymorphism may be a prognostic factor for PSA recurrence after radical prostatectomy.

Haplotypes, loss of heterozygosity, and expression levels of glycine N-methyltransferase in prostate cancer.

PURPOSE: Glycine N-methyltransferase (GNMT) affects genetic stability by regulating DNA methylation and interacting with environmental carcinogens. In a previous study, we showed that GNMT acts as a susceptibility gene for hepatocellular carcinoma. Here, we report on our efforts to characterize the haplotypes, loss of heterozygosity (LOH), and expression levels of the GNMT in prostate cancer. EXPERIMENTAL DESIGN: Peripheral blood mononuclear cell DNA collected from 326 prostate cancer patients and 327 age-matched controls was used to determine GNMT haplotypes. Luciferase reporter constructs were used to compare the promoter activity of different GNMT haplotypes. GNMT LOH rates in tumorous specimens were investigated via a comparison with peripheral blood mononuclear cell genotypes. Immunohistochemical staining was used to analyze GNMT expression in tissue specimens collected from 5 normal individuals, 33 benign prostatic hyperplasia patients, and 45 prostate cancer patients. RESULTS: Three major GNMT haplotypes were identified in 92% of the participants: A, 16GAs/DEL/C (58%); B, 10GAs/INS/C (19.9%); and C, 10GAs/INS/T (14.5%). Haplotype C carriers had significantly lower risk for prostate cancer compared with individuals with haplotype A (odds ratio, 0.68; 95% confidence interval, 0.48-0.95). Results from a phenotypic analysis showed that haplotype C exhibited the highest promoter activity (P < 0.05, ANOVA test). In addition, 36.4% (8 of 22) of the prostatic tumor tissues had LOH of the GNMT gene. Immunohistochemical staining results showed abundant GNMT expression in normal prostatic and benign prostatic hyperplasia tissues, whereas it was diminished in 82.2% (37 of 45) of the prostate cancer tissues. CONCLUSIONS: Our findings suggest that GNMT is a tumor susceptibility gene for prostate cancer.

CDKN1B V109G polymorphism frequency and prostate cancer risk in Taiwan.

AIM: The CDKN1B (p27) V109G polymorphism has been suggested to confer the risk of advanced prostate cancer in Caucasian males. However, its prevalence in Asian populations has never been reported. The aim of this study was to determine the CDKN1B V109G polymorphism frequency in the low incidence Taiwanese population and investigate its potential role on prostate cancer susceptibility and disease progression. METHODS: A hospital-based case-control study was conducted, which enrolled a total of 190 prostate cancer patients and 292 age-matched male controls. PCR-RFLP was used to determine the CDKN1B V109G polymorphism. The association between CDKN1B V109G and prostate cancer risk and clinicopathologic variables was analyzed. RESULTS: The variant CDKN1B G allele frequency in Taiwanese males appears to be low (2.1%). Overall, there was no significant association between CDKN1B V109G polymorphism and prostate cancer risk. Similarly, no significant findings were found when further stratified by different age groups, disease stages, and pathological grades. In terms of disease outcome, the CDKN1B V109G genotypes were not associated with either hormone response status after hormone therapy (p = 0.730) or with prostate-specific antigen recurrence for clinically localized prostate cancer patients who receive radical prostatectomy (p = 0.536). CONCLUSIONS: There was a low prevalence of CDKN1B V109G polymorphism in Taiwanese compared to Caucasian males. Hence, it may not be an appropriate biomarker of prostate cancer among the Taiwanese population. Further large-scale studies are needed to clarify the role of CDKN1B V109G polymorphism on prostate cancer risk.

Ureterosciatic hernia causes obstructive uropathy.

Obstructive uropathy can be caused by urolithiasis, fibrotic ureteral stricture, inflammatory ureteritis with polyp formations, ureteral malignancy and various forms of external compression. Ureteral herniation is a relatively rare cause of obstructive uropathy and has been reported with herniation sites including inguinal canal, femoral canal and sciatic foramen. Most ureteral herniations occur in the inguinal area. In the literature, previous cases of sciatic ureter have been treated with observation in asymptomatic patients or with surgery in patients with obstructive uropathy or clinical symptomatology. We report the case of a 91-year-old female with asymptomatic hydronephrosis of the left kidney due to extremely rare ureterosciatic herniation. Her global renal function was acceptable. As she was elderly and a poor surgical candidate, watchful waiting was recommended after discussion with the patient and her family.

Changes of Bladder M1,3 Muscarinic Receptor Expression in Rats Fed with Short-Term/Long-Term High-Fat Diets.

OBJECTIVES: To investigate the effect of high-fat diet (HFD) on bladder M1,3 muscarinic receptor expression and contractile function in the rat. METHODS: Eight-week-old male rats were divided into two groups including one with HFD for 8 weeks (short-term) and the other for 24 weeks (long-term). Each group was compared to age-matched rats fed with normal chow as controls. The body weight, food intake amount and blood biochemistry were monitored. Bladder muscle contractile responses to acetylcholine (0.1-10 µM), bethanechol (10 µM) and KCl (50 mM) were studied in an organ bath set-up. Bladder M1 and M3 muscarinic receptor protein expressions were measured by Western blotting analysis. RESULTS: Increase in body weight as well as blood triglyceride, cholesterol and sugar levels compared to controls were noted in both 8- and 24-week HFD rats. Eating appetite change with increased food and water intakes was noted in the HFD rats. Significantly decreased bladder contractile responses to acetylcholine and bethanechol were shown in both HFD groups. On the other hand, decreased bladder contractile response to KCl was demonstrated in the 24-week group but not the 8-week group. The expressions of bladder M1 and M3 muscarinic receptor proteins were significantly and progressively decreased by HFD feeding from 8 to 24 weeks. CONCLUSIONS: High-fat diet induces obesity and polyphagia in rats. Short-term and long-term HFD feeding decrease rat bladder M1 and M3 receptor expressions as well as contractile responses to the agonistic stimulation. In addition, bladder muscle dysfunction develops after long-term HFD feeding.

KChIP3: a binding protein for Taiwan banded krait beta-bungarotoxin.

Using B1 chain of beta-bungarotoxin (beta-Bgt) as bait in yeast two-hybrid screen, we found that KChIP3 was a binding protein of B1 chain. Thus, protein-protein interaction between beta-Bgt and KChIP3 is investigated in the present study. Pull-down assay showed that recombinant KChIP3 proteins were associated with beta-Bgt as well as B1 chain, whereas the inability of KChIPs 1, 2 and 4 to bind with beta-Bgt was observed. Although Ca2+ was not a crucial factor essential for the binding of KChIP3 with beta-Bgt and B1 chain, their interaction could be enhanced by the addition of Ca2+. Alternatively, the association of A1 chain of beta-Bgt with KChIP3 was marginally detected. The dissociation constant of beta-Bgt with KChIP3 were 12.2 and 6.08 microM in the absence and presence of 2mM Ca2+, respectively. Moreover, native KChIP3 from rat brain was to be isolated by beta-Bgt-Sepharose. These observations indicate that KChIP3 is a binding protein of beta-Bgt. In view of the multiple functions of KChIP3 in neuronal cells, the interaction of KChIP3 with beta-Bgt may represent an event for the manifestation of the biological activities of beta-Bgt.

Correlation of p53 protein accumulation and Bcl-2 overexpression with histopathological features in prostatic cancer.

BACKGROUND AND PURPOSE: p53 mutation and Bcl-2 overexpression is correlated with advanced prostate cancer. This study investigated the correlation of p53 and Bcl-2 immunoreactivity frequency with histopathological features in patients with prostate cancer in Taiwan. METHODS: Primary adenocarcinomas from 125 radical prostatectomy specimens were stained using commercial monoclonal antibodies. Association between immunohistochemical findings and tumor extent, Gleason score and preoperative prostate-specific antigen (PSA) levels were assessed. RESULTS: Abnormal p53 expression was identified in 44 tumors (35.2%) and was correlated with high serum PSA (p=0.022) and advanced disease (p=0.005), but not Gleason score. Ten tumors (8%) expressed Bcl-2. A significant positive association was found between Bcl-2 and PSA (p=0.034). There was no association between p53 and Bcl-2 immunopositivity. CONCLUSIONS: p53 mutation was positively correlated with serum PSA and tumor extent. Overexpression of Bcl-2 was associated with high serum PSA only.

p53 Codon 72 and p21 codon 31 polymorphisms in prostate cancer.

The tumor suppressor gene p53 and its downstream effector p21 are thought to play major roles in the development of human malignancy. Polymorphic variants of p53 at codon 72, and p21 at codon 31, have been found to be associated with cancer susceptibility, but few studies have investigated their effect on prostate cancer risk. In this case-control study, we investigated the association of p53 codon 72 and p21 codon 31 polymorphisms with prostate cancer risk in a Taiwanese population. In total, 200 patients with prostate cancer, 247 age-matched male controls, and 181 non-age-matched symptomatic benign prostatic hyperplasia (BPH; American Urological Association symptom score > or = 8 and prostate volume > 20 gm) recruited from two medical centers in southern Taiwan were genotyped. Overall, we found no significant association between p53 polymorphism and risk of prostate cancer. However, for p21 polymorphism, the frequencies of p21 Ser/Ser, Ser/Arg and Arg/Arg were 52 (26.0%), 85 (42.5%), 63 (31.5%) in case patients, 48 (26.5%), 82 (45.3%), 51 (28.2%) in BPH patients, and 76 (30.8%), 119 (48.2%), 52 (21.1%) in controls, respectively. Among the prostate cancer cases and controls, subjects with Arg/Arg genotype were found to have a 1.78-fold increased risk [95% confidence interval (CI), 1.06-3.01] of developing prostate cancer compared with those having the Ser/Ser genotype, after adjusting for other potential covariates. This significant association was slightly stronger [odds ratio (OR), 2.13; 95% CI, 1.16-3.92] in younger men (< or = 72 years; n = 99 and 126 for cases and controls, respectively) and correlated with localized disease stage (OR, 1.96; 95 % CI, 1.15-3.35) and moderately differentiated prostate cancer (OR, 2.04; 95% CI, 1.17-3.53). In addition, the Arg/Arg genotype was associated with BPH risk in those with large prostate volumes (> 50 mL) compared with those having the Ser/Ser genotype [OR, 2.29; 95% CI, 1.07-4.98]. Our findings suggest that the p21 codon 31 polymorphism may be associated with the development of prostate enlargement and cancer.

Association between vitamin D receptor polymorphisms and prostate cancer risk in a Taiwanese population.

Recent molecular epidemiological studies have shown that the inherited polymorphisms of VDR gene may be linked to prostate cancer risk and its aggressive phenotypes. However, the findings remain inconclusive. In this study, we investigated the association of the BsmI, ApaI and TaqI polymorphisms of VDR gene with prostate cancer risk in a Taiwanese population. In total, 160 prostate cancer patients and 205 age-matched male controls were studied between December 2000 and February 2003. No significant associations were found between the ApaI and TaqI polymorphisms and the risk of prostate cancer. However, the control group was found to have a significantly higher frequency of the BsmI 'BB' and 'Bb' genotypes (15.6%) than prostate cancer patients (8.1%). After adjustment for age, patients with BsmI 'BB' or 'Bb' genotypes were associated with a twofold decreased risk (OR = 0.50; 95% CI = 0.25-0.98; P = 0.045) for developing prostate cancer than those with 'bb' genotypes. This effect was particularly significant among men below the median age of 72 years (P = 0.017). Moreover, stronger associations were found in the advanced stages (T3/T4/N1/M1) and poorly differentiated disease (Gleason score >/= 7) ('BB' and 'Bb' vs 'bb': OR = 0.25; 95% CI = 0.07-0.83; P = 0.024 and OR = 0.25; 95% CI = 0.07-0.85; P = 0.026, respectively). Our findings suggest that the VDR BsmI polymorphism may play a significant role in the development of prostate cancer.