Serum triiodothyronine is increased in men with prostate cancer and benign prostatic hyperplasia

Triiodothyronine is the active thyroid hormone produced by de-iodination of the precursor thyroxine that is necessary for the growth of prostate cancer cells in vitro. For this reason we assessed serum triiodothyronine levels in men with localized prostate cancer, benign prostatic hyperplasia (BPH) and controls in the same age group.

Materials and Methods

We studied 161 men referred for treatment of localized prostate cancer, 20 with BPH and 27 controls. Serum triiodothyronine was determined by fluorometric immunoassay and a commercially available instrument.

Results

Men with BPH had the highest triiodothyronine levels, followed by those with prostate cancer. Controls had the lowest triiodothyronine. There was significant triiodothyronine variation among the 3 groups (1-way ANOVA p = 0.001). In men with BPH serum triiodothyronine was significantly different from that in men with prostate cancer (Tukey’s multiple range test p = 0.013). Men with prostate cancer had serum triiodothyronine that was significantly different than in controls (p = 0.048), as did those with BPH (p <0.001). Because serum triiodothyronine normally decreases with age, we performed multivariate analysis of variance controlling for age. There was a significant decrease in serum triiodothyronine with age (p = 0.020). There was also significant triiodothyronine variation among the 3 subject groups independent of age (p <0.001).

Conclusions

Urologists are actively seeking additional biomarkers of prostate cancer aggressiveness. Many prostate cancers are quite indolent and may never cause a problem but it is impossible to identify such tumors with certainty. With more and better biomarkers many older men with prostate cancer may be spared the rigors of radiation therapy and/or surgery as well as complications. Triiodothyronine may be such a biomarker. Also, new prostate cancer and BPH therapies may be directed toward inhibiting the mitogenic effects of triiodothyronine.     

Serum keratinocyte growth factor measurement in patients with prostate cancer

PURPOSE: Keratinocyte growth factor (KGF) is a stromally derived growth factor important in mediating androgen induced activities in benign prostatic hyperplasia (BPH) and prostate cancer. We assessed whether serum KGF could be used as a molecular marker in patients with prostate cancer. MATERIALS AND METHODS: Using a modified double sandwich enzyme-linked immunosorbent assay, we measured serum KGF in 56 men with prostate cancer and 81 men with BPH. Comparative analyses were made with total serum prostate specific antigen (PSA), disease stage and clinical grade. RESULTS: Following optimization, a sensitive and reproducible assay for serum KGF measurement was developed. Serum KGF levels tend to be higher in men with BPH compared to those with prostate cancer (1,242 and 828 pg./ml., respectively). A weak but significant linear relationship between PSA and KGF (p = 0.034) was found in patients with BPH. There was no association between KGF and tumor grade or stage but there was a strong positive linear relationship between PSA and KGF (p = 0.006, R(2) = 68.3%) in low grade tumors. In those men with serum PSA less than 10 ng./ml. KGF levels were significantly higher in BPH compared to prostate cancer cases (965 +/- 245 and 133 +/- 61.3 pg./ml., respectively, p = 0.0058). Using a KGF threshold range of 500 to 900 pg./ml., specificity for detecting BPH was 88% to 100% and the positive predictive value was 92% to 100%. CONCLUSIONS: We have optimized a reproducible and sensitive enzyme-linked immunosorbent assay system for the measurement of serum KGF. Overall KGF levels tend to be lower in patients with prostate cancer than with BPH. In patients with serum PSA less than 10 ng./ml. serum KGF levels were significantly higher in the BPH compared to the prostate cancer group. A large prospective study is indicated to assess the role of serum KGF measurement in patients with prostate cancer.     

High serum prostate-specific antigen levels in the absence of prostate cancer in Middle-Eastern men: the clinician's dilemma

OBJECTIVE: To investigate the common causes of total serum prostate-specific antigen (PSA) values of> 10 ng/mL in an Arab population, as in the USA and Europe the risk of prostate cancer is considered high in men with such PSA levels. PATIENTS AND METHODS: Serum total PSA was measured in men presenting to our hospital as part of the investigation for prostate cancer screening and/or in elderly men with prostatism. Men with a serum PSA level of> 10 ng/mL were further investigated by transrectal ultrasonography (TRUS) of the prostate and biopsy of suspicious lesions for histological diagnosis. In addition, the percentage of free PSA, PSA velocity and PSA density were determined. All the patients included in this study were men of Arab origin residing in Kuwait. RESULTS: In all, 1700 men (mean age 55.6 years, range 35-94) were assessed; of these, 161 had a serum PSA of> 10 ng/mL, attributable to benign prostatic hyperplasia (BPH) in 110 (68%), BPH with histological features of prostatitis in 33 (21%) and prostate cancer in 18 (11%). TRUS of the prostate in 143 of the 161 men with either BPH or BPH with prostatitis showed varying grades of intraprostatic calcifications in 22 (15%). Both PSA density and percentage free PSA did not contribute to determining the causes of total PSA levels of> 10 ng/mL. There was a progressive decline in PSA in all patients with BPH and prostatitis, except one who at re-biopsy had prostate cancer (T1N0M0, G1). CONCLUSION: Total PSA values of> 10 ng/mL in Arab men may be a result of BPH, BPH with prostatitis or prostate cancer, in that order. A gradual decline in total PSA (decreased PSA velocity) with time to < 4 ng/mL often confirms the diagnosis of BPH with prostatitis. The percentage of free PSA and PSA density may not be helpful in diagnosing prostate cancer with certainty in these patients. Compared with Caucasians in the USA and Europe, BPH and BPH with prostatitis appear to be more frequent causes of serum PSA levels of> 10 ng/mL in Arab men.     

C-reactive protein is significantly associated with prostate-specific antigen and metastatic disease in prostate cancer

OBJECTIVE: To further analyse the relationship of c-reactive protein (CRP) levels to prostate cancer, by measuring CRP in men with prostate cancer and benign prostatic hypertrophy (BPH), as chronic inflammation has long been linked to cancers with an infectious cause and CRP is a nonspecific marker for inflammation, associated with prostate cancer incidence and progression. PATIENTS AND METHODS: Data from 114 men, most of whom had had radioactive seeds implanted, were evaluated from November 1990 to April 2002. In addition, 27 men were included who had biopsy-confirmed BPH. CRP was assessed with an automated chemiluminometric high-sensitivity assay kit. RESULTS: There was no significant difference in CRP levels in men with localized prostate cancer or BPH but levels were significantly higher in men with bone metastases. There was also a significant correlation of CRP level with prostate-specific antigen (PSA) in those with cancer. Because PSA is correlated with disease stage, multiple linear regression was used with CRP as the dependent variable, and PSA and disease stage as independent variables. The regression was significant overall (P < 0.001) and the effect of disease stage on CRP (P < 0.001) was independent of the effect of PSA level (P = 0.001). CONCLUSION: The strong association of CRP with PSA, independent of tumour stage, suggests that inflammation might be fundamental in prostate cancer, and that chronic inflammation may be a legitimate target for prostate cancer chemoprevention and treatment.     

SELDI protein profiling of dunning R-3327 derived cell lines: identification of molecular markers of prostate cancer progression

BACKGROUND: We recently demonstrated the protein expression profiling of Dunning rat tumor cell lines of varying metastatic potential (G (0%), AT-1 ( approximately 20%), and MLL (100%)) using SELDI-TOF-MS. As a parallel effort, we have been pursuing the identification of the protein(s) comprising the individual discriminatory "peaks" and evaluating their utility as potential biomarkers for prostate cancer progression. METHODS: To identify the observed SELDI-TOF-MS m/z (mass/charge) values with discriminatory expression between different sublines, we employed a combination of chemical pre-fractionation, liquid chromatography, gel electrophoresis and tandem mass spectroscopy. Identified proteins were then verified by immuno-assay and Western analysis. RESULTS: A 17.5 K m/z SELDI-TOF-MS peak was found to retain discriminatory value in each of two separate study-sets with an increased expression in the metastatic MLL line. Sequence identification and subsequent immunoassays verified that Histone H2B is the observed 17.5 K m/z SELDI peak. SELDI-based immuno-assay and Western Blotting revealed that Histone H2B is specifically over-expressed in metastatic MLL lines. CONCLUSIONS: SELDI-TOF MS analysis of the Dunning prostate cancer cell lines confirmed the consistent overexpression of a 17.5 K m/z peak in metastatic MLL subline. The 17.5 kDa protein from MLL has been isolated and identified as Histone H2B.     

Significance of vitamin D receptor gene polymorphism for risk and disease severity of prostate cancer and benign prostatic hyperplasia in Japanese

OBJECTIVE: Recent studies have demonstrated an association between vitamin D receptor (VDR) genotype and prostate cancer. Currently, there is a scarcity of data regarding the association of VDR genotype with benign prostatic hyperplasia (BPH). The purpose of this study was to investigate the TaqI VDR polymorphism in Japanese prostate cancer patients, Japanese BPH patients and Japanese controls in order to determine if an association exists between VDR genotype and the risk of developing prostate cancer and BPH as well as disease severity. METHODS: 110 prostate cancer patients, 83 BPH patients and 90 male age-matched controls were genotyped for a previously described TaqI restriction fragment length polymorphism at codon 352 in exon 9 of the VDR gene. Products were digested into T allele or t allele according to the absence or presence of a TaqI restriction site with individuals being classified as TT, Tt or tt. RESULTS: The frequency of the genotype tt was higher in the control group (6.7%) compared to patients with prostate cancer (1.8%) and BPH (3.6%) but this was not statistically significant. However, the frequency of the genotype TT was significantly higher among prostate cancer patients with locally advanced or metastatic disease (T3/ T4/N1/M1) compared to controls (p = 0.001). In addition, the genotype TT was significantly higher among prostate cancer patients with a high Gleason grade of tumor (grade 5) compared to controls (p = 0.0001). In addition, the genotype TT was statistically higher in BPH patients with high prostate volume (volume >50 cm(3)) compared to controls (p = 0.001). CONCLUSION: These data demonstrate that VDR genotype plays an important role in determining the risk of more advanced and aggressive prostate cancer as well as prostatic enlargement in Japanese men.     

Association of V89L SRD5A2 polymorphism with prostate cancer development in a Japanese population

PURPOSE: The SRD5A2 gene codes the steroid 5-reductase type II, a critical mediator of androgen action, and the V89L and A49T polymorphisms of this gene may be associated with a distinct enzyme activity. We explored the association among these polymorphisms and the risk of prostate cancer or benign prostatic hyperplasia (BPH) in a Japanese population. MATERIALS AND METHODS: This study included 302 patients with prostate cancer, 228 with BPH and 243 male controls. V89L and A49T polymorphisms were analyzed by the polymerase chain reaction restriction fragment length polymorphism method. Genotypes were evaluated by electrophoresis on agarose gel. RESULTS: For the V89L polymorphism there were no significant differences in genotype frequencies in patients with prostate cancer and controls (p = 0.071) or in patients with BPH and male controls (p = 0.219). However, males with the VV or VL genotype were at significantly increased risk for prostate cancer compared with those with the LL genotype (adjusted OR 1.69, 95% CI 1.07 to 2.65, p = 0.024). The risk of BPH in males with the VV or VL genotype was not significantly elevated in comparison with those with the LL genotype (adjusted OR 1.37, 95% CI 0.85 to 2.20, p = 0.194). The V89L variant was not associated with the grade or stage of prostate cancer, or with patient age. For the A49T polymorphism all subjects had the AA genotype. CONCLUSIONS: The V allele of the V89L polymorphism in the SRD5A2 gene may dominantly increase the risk of prostate cancer.     

过氧化物酶体增殖激活物受体与15-脂氧合酶-2在前列腺癌组织中的表达及其意义

目的 观察过氧化物酶体增殖激活物受体(PPAR-γ)及15-脂氧合酶-2(15-LOX-2)在前列腺癌中的表达,探讨其意义.方法 采用免疫组织化学方法检测28例前列腺癌组织中PPAR-γ及15-LOX-2蛋白的表达,取26例前列腺增生组织作为对照.结果 PPAR-γ在前列腺癌组表达阳性程度高于前列腺增生组(x2=4.84,P＜0.05);15-LOX-2在前列腺癌组表达阳性程度低于前列腺增生组(x2 =9.00,P＜0.05).T3期前列腺癌PPAR-γ的表达阳性程度明显高于T2期(H=4.103,P＜0.05);T2期与T3期前列腺癌细胞15-LOX-2的表达阳性程度差异无统计学意义(H =0.076,P＞0.05).Gleason评分≥7分前列腺癌PPAR-γ的表达阳性程度明显高于Gleason评分＜7分(H=5.306,P＜0.05);Gleason评分≥7分与Gleason评分＜7分前列腺癌15-LOX-2的表达阳性程度差异无统计学意义(H =0.313,P＞0.05).结论 PPAR-γ蛋白在前列腺癌组织中高表达,并且与病理分期及Gleason评分有关;15-LOX-2在前列腺癌组织中低表达.它提示PPAR-γ和15-LOX-2与前列腺癌发生与发展有关.     

The ability of systematic transrectal ultrasound guided biopsy to detect prostate cancer in men with the clinical diagnosis of benign prostatic hyperplasia.

Multiple directed and systematic ultrasound guided biopsies of the prostate were performed in 73 men with the clinical diagnosis of benign prostatic hyperplasia (BPH). Seven men (10%) had prostate cancer. Of the 67 patients with benign biopsies 40 underwent subsequent transurethral prostatectomy and 2 (5%) had prostate cancer. Multiple directed and systematic biopsies of the prostate detected 78% of the nonpalpable prostate cancers diagnosed in the study population. Radical prostatectomy was performed in all 9 men with prostate cancer: there were 3 small organ-confined tumors, 5 large organ-confined tumors and 1 stage C tumor with 1 focus of microscopic capsular penetration. Our results suggest that multiple directed and systematic ultrasound guided biopsies are capable of detecting low volume nonpalpable prostate cancer in men with BPH. However, the exact indication for pre-treatment ultrasound guided biopsy of the prostate in men with symptomatic BPH remains unclear. It may be that use of this modality is most appropriate for patients undergoing pharmacological therapy or balloon dilation of BPH rather than for those undergoing transurethral prostatectomy.     

Insulin-like growth factors and risk of benign prostatic hyperplasia

BACKGROUND: Insulin-like growth factors (IGFs) have potent growth mitogenic and anti-apoptotic effects on prostate tissue, whereas IGF binding proteins (IGFBPs) inhibit growth of prostatic tissue. The IGF axis has been implicated in prostate cancer risk, but its role in benign prostatic hyperplasia (BPH) is unclear. METHODS: Plasma levels of IGF-I, IGF-II, IGFBP-1, and IGFBP-3 were determined from the fasting bloods of 206 BPH cases admitted for treatment and 306 randomly selected population controls in Shanghai, China. RESULTS: Relative to the lowest tertile, men in the highest tertile of IGF-I levels had a significantly elevated risk of BPH (odds ratio [OR] = 2.80, 95% confidence interval [95% CI] = 1.60-4.92; P(trend) < 0.001). Results for IGF-I were more pronounced after adjustment for serum androgens. In contrast, men in the highest IGFBP-3 tertile had a significantly reduced risk (OR = 0.40; 95% CI = 0.23-0.69; P(trend) < 0.001). No associations of BPH with IGF-II and IGFBP-1 were observed. CONCLUSION: As has been previously observed for prostate cancer, we found that IGF-I and IGFBP-3 are associated with BPH risk in China. Further investigation is needed to elucidate the role of the IGF axis in BPH etiology.     

The early detection research network surface-enhanced laser desorption and ionization prostate cancer detection study: A study in biomarker validation in genitourinary oncology

Prostate-specific antigen (PSA) screening has led to a dramatic increase in prostate cancer detection with a concurrent stage migration. Although the test has revolutionized prostate cancer detection by identifying disease that is potentially curable in the majority of men, only 25% of men receiving test results of PSA > 4 ng/ml will have prostate cancer and many men receiving a normal PSA will have disease, including high-grade disease. There is a need for improved biomarkers for detecting prostate cancer. One such method of cancer detection is surface-enhanced laser desorption and ionization (SELDI). The Early Detection Research Network (EDRN) validation study for SELDI for prostate cancer is described. In a three-stage study, the portability and reproducibility of the technique will be determined; the predictive algorithm will be refined in a multi-institutional case-control population; followed by ultimate validation in the context of a prospective trial with complete disease ascertainment. The unique aspect of the EDRN SELDI validation study is the novel use of two groups of cancer cases: those cases with higher-risk disease (Gleason > or = 7) and those cases with lower-risk disease (Gleason < or = 6). This study will allow the first evaluation of a predictive algorithm that includes prognosis in disease screening. The EDRN SELDI prostate cancer biomarker validation study is a rigorous evaluation of a new detection method for prostate cancer. The methodologies used for this evaluation will prove useful for guiding future biomarker studies in this challenging disease.     

Serum hepatocyte growth factor activator (HGFA) in benign prostatic hyperplasia and prostate cancer

OBJECTIVES: Hepatocyte growth factor activator (HGFA) is responsible for proteolytic activation of the precursor form of hepatocyte growth factor (HGF). We attempted to clarify whether serum levels of HGFA could be used as a marker for prostate cancer. MATERIAL AND METHODS: Serum levels of total HGF and HGFA were measured by enzyme-linked immunosorbent assay in 99 healthy controls, 27 patients with benign prostatic hyperplasia (BPH) and 119 patients with prostate cancer. RESULTS:: The mean+/-S.D. serum levels of HGFA in untreated prostate cancer and BPH cases were 0.42+/-0.24 and 0.50+/-0.26 ng/ml, respectively (no significant difference). Serum HGFA was significantly elevated in hormone-refractory prostate cancer (stage D3) compared to other stages, while HGF did not significantly differ with regard to clinical stage. CONCLUSIONS: Serum HGFA tends was elevated in patients with advanced stage prostate cancer. Further studies in large groups of patients are needed to clarify the clinical value of HGFA.     

Free and total prostate-specific antigen levels in saliva and the comparison with serum levels in men

OBJECTIVE: We investigated free and total prostate-specific antigen (PSA) levels and free/total (f/t) ratio in the fasting saliva and compared them with the serum levels in normal individuals, in patients with benign prostatic hyperplasia (BPH) and prostate cancer. Our aim was to determine free and total PSA and f/t ratio in saliva and to improve and simplify the differentiation between BPH and prostate cancer by using saliva as an alternative to serum. METHODS: Serum and fasting saliva concentrations of free and total PSA were measured in 35 men with BPH, 16 men with stage D prostate cancer, and 25 healthy men. Serum and fasting saliva samples were collected at the same time and were analyzed on the same day at our laboratory with microparticle enzyme immunoassay technology. RESULTS: For the total of 76 men, there was a significant correlation between free and total PSA levels in each sample (r = 0.97 for serum and r = 0.44 for saliva, p<0.001). Although there was a significant difference between three groups for serum-free and total PSA levels and serum f/t ratios, no significant difference was determined between groups for salivary free and total PSA levels and salivary f/t ratios. No correlations were found between patient age and salivary PSA levels. CONCLUSIONS: Fasting salivary free and total PSA levels are not effected by high serum levels of prostatic origin. Although there was a significant difference between mean serum and salivary levels of free and total PSA in each group, the f/t ratio of saliva was very close to the serum ratio of normal subjects. Determination of free and total PSA in saliva to improve and simplify the differentiation between prostate cancer and BPH is not suitable for use as alternative measurement of serum.     

Plasma concentrations of metalloproteinases (MMP-1, MMP-3) and their inhibitors in patients with prostate cancer

Summary Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are involved in important processes of tumor invasion and metastasis. In the study presented, matrix metalloproteinase 1 (MMP1) and 3 (MMP3), the tissue inhibitor of metalloproteinase 1 (TIMP1) and the complex MMP1/TIMP1 were measured by ELISA tests specific for these proteins in blood plasma. These components have been investigated in prostate cancer patients (PCa) with metastases (n = 18; T2, 3, 4 pN1, 2M1), prostate cancer patients without metastases (n = 29; T2, 3 pN0M0), patients with benign prostate hyperplasia (BPH; n = 29) and in healthy men (n = 35). Mean values of MMP1 and of the complex MMP1/TIMP1 were not different among the four groups. The mean values of MMP3 and especially TIMP1 were significantly higher in prostate cancer patients with metastases compared with controls, BPH patients and prostate cancer patients without metastases. Ten of these 18 patients had TIMP1 levels higher than the upper reference limit. TIMP1 concentrations correlate to the tumor stage but not to the tumor grade. These results indicate, that TIMP1 could be an potential marker for metastases in prostate cancer patients.      

Clinical stage T1c prostate cancer: pathologic outcomes following radical prostatectomy in black and white men

BACKGROUND: The incidence of prostate cancer in black men is 50% to 70% higher than among age-matched white men. Black men have a twofold higher mortality rate and overall tend to have higher serum prostate-specific antigen (PSA) levels than white men. To determine whether racial differences exist in men whose prostate cancer was diagnosed based solely on an elevated serum PSA level, we compared clinical and pathologic features in black and white men undergoing radical prostatectomy (RP) for clinical stage T1c prostate cancer. METHODS: We used a prospectively collected database to identify all men undergoing RP for clinical T1c prostate cancer between July 1995 and October 2000. A total of 129 consecutive men (56 black men and 73 white men) were compared for age at diagnosis, serum PSA level, biopsy Gleason score, pathologic stage, RP specimen Gleason score, incidence of lymph node metastasis, and incidence of positive surgical margins. RESULTS: Statistically significant differences were not found by race in patients' ages, serum PSA levels, biopsy Gleason score, pathologic stage, incidence of lymph node metastases, or incidence of positive surgical margins. The RP specimen Gleason score was more heterogeneous in black men than white men (P=0.02). CONCLUSIONS: Racial differences in the incidence and mortality rate of prostate cancer are well known, but differences in the clinical and pathologic features between black and white men with prostate cancer identified solely based on an elevated serum PSA level with negative results on digital rectal examination (clinical stage T1c ) have been poorly studied. Our results suggest that men with clinical stage T1c prostate cancer have similar clinical and pathologic findings regardless of race. These results suggest that early-detection programs using serum PSA testing for prostate cancer in black men potentially can result in improvements in prostate cancer outcomes in this high-risk group.     

Pilot and feasibility study of serum chemokines as markers to distinguish prostatic disease in men with low total serum PSA

BACKGROUND: The incidence and prevalence of both benign prostatic hypertrophy (BPH) and prostate cancer (PCa) increase with the aging process. Our laboratory recently showed that the chemokines CXCL5 and CXCL12, which normally function as inflammatory mediators, are secreted at higher levels by aging prostate stromal fibroblasts and elicit proliferative responses from both prostate stromal fibroblast and epithelial cells. Because both CXCL5 and CXCL12 are secreted molecules, we hypothesized that their levels in patient serum might serve as biomarkers to distinguish between BPH and PCa. METHODS: Serum CXCL5 and CXCL12 levels were determined using sandwich ELISAs for 51 men demonstrating low serum PSA values of < or =10 ng/ml who underwent diagnostic needle biopsy for the detection of PCa. The bivariate relationship of circulating chemokine levels, age, and disease status in the prostate was tested using the Wilcoxon rank-sum test. RESULTS: Total serum CXCL12 levels were significantly higher for men who were biopsy positive compared to those who were biopsy negative for cancer and histological prostatitis (P = 0.050). Among men who were biopsy negative for PCa, total serum CXCL5 levels were inversely associated with prostate volume and were significantly higher in men with concomitant BPH and histological prostatitis compared to those without evidence of prostatic disease (P < 0.003). CONCLUSIONS: The results of this pilot and feasibility study suggest that serum or plasma CXCL5 and CXCL12 levels may potentially distinguish between BPH and PCa among patients presenting with low serum PSA, and may be useful toward facilitating decisions to perform diagnostic needle biopsy in this patient population.     

Evidence of a novel biomarker, alphas1-Casein, a milk protein, in benign prostate hyperplasia

Benign prostate hyperplasia (BPH) is a common disease in elderly men. Although it is a non-malignant disease, it has a significant detrimental impact on the quality of life in patients with late-stage disease. Owing to the lack of specific markers, diagnosis of early-stage BPH has been proven unsuccessful. Recently, using two-dimensional electrophoresis, we identified a group of prostatic secretory proteins that are specifically produced by BPH cells (Xu et al., Electrophoresis 2003; 24: 1311). In this study, we investigated the potential diagnostic value of one of the secretory proteins, alphas1-Casein, in BPH by inmmunohistological staining of normal, BPH and prostate cancer tissues. We found that 90% (20 out of 22) of BPH tissues showed moderate to strong alphas1-Casein protein expression whereas none of the normal tissues (0 out of 10) and less than 10% of the prostate cancer tissues (3 out of 30) showed similar staining intensity. Our results suggest that alphas1-Casein may be a potential biomarker for early identification of BPH patients.     

Calculated fast-growing benign prostatic hyperplasia--a risk factor for developing clinical prostate cancer

OBJECTIVE: Whether there is an association between the development of benign prostatic hyperplasia (BPH) and clinical prostate cancer is controversial. The present report tests the hypothesis of an association between BPH growth and the development of clinical prostate cancer by examining stage, grade and PSA-level in men with recently discovered clinical prostate cancer with slow or fast-growing BPH. If the hypothesis is true, men with fast-growing BPH would have a more advanced clinical prostate cancer. MATERIAL AND METHODS: Two hundred and twenty patients in whom a clinical prostate cancer was diagnosed were consecutively included. The prevalence of atherosclerotic disease, non-insulin-dependent diabetes mellitus (NIDDM) or treated hypertension was provided by the respective patient's medical history. Tallness, body weight, waist measurement, hip measurement and blood pressure were determined. The body mass index (BMI) and waist/hip ratio (WHR) were calculated. Blood samples were drawn to determine triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, ALAT and the fasting plasma insulin level. The prostate gland volume was measured using transrectal ultrasound. The annual BPH growth rate was calculated, assuming that the total prostate gland volume was 20 mL at the patient age of forty. The prostate cancer diagnosis was established using the technique of transrectal ultrasound-guided automatic needle biopsy of the prostate. RESULTS: Men with clinical prostate cancer, PSA <50 ng/mL, and with fast-growing BPH had a higher systolic (p = 0.009) and diastolic (p = 0.020) blood pressure, were taller (p < 0.001) and more obese, as determined by body weight (p < 0.001), BMI (p = 0.005), waist measurement (p < 0.001) and hip measurement (p = 0.003). They also had a higher fasting plasma insulin level (p = 0.014) and a lower HDL-cholesterol level (p = 0.067) than men with slow-growing BPH. Moreover, men with clinical prostate cancer, PSA <50 ng/mL, and fast-growing BPH had more pronounced clinical prostate cancer, as measured by grade (p = 0.029) and PSA-level (p = 0.016), than men with slow-growing BPH. In the total material, including men with clinical prostate cancer, PSA >/=50 ng/mL, men with fast-growing BPH also had a higher prevalence of NIDDM (p = 0.039) and a borderline statistical significance for higher stage (p = 0.09) than men with slow-growing BPH. The BPH growth rate was significantly associated with the clinical prostate cancer grade (p = 0.018) and PSA-level (p = 0.002) but not with the clinical cancer stage in a multivariate statistical analysis. CONCLUSIONS: This report confirms findings in previous studies that fast-growing BPH is a risk factor for NIDDM, hypertension, tallness, obesity, dyslipidaemia and hyperinsulinaemia. The present report extends this list of risk factors to include atherosclerotic disease manifestations, hyperuricaemia and higher ALAT levels. The study suggests that fast-growing BPH is a risk factor for developing clinical prostate cancer and, thus, supports the hypothesis of an association between the development of BPH and clinical prostate cancer. The study generates the hypothesis that clinical prostate cancer is a component of the metabolic syndrome and that insulin is a promoter of clinical prostate cancer.     

Serum Interleukin-11 in Patients with Benign Prostatic Hyperplasia and Prostate Cancer

To clarify whether serum levels of interleukin-11 (IL-11) could be a useful marker in patients with prostate cancer, serum IL-11 was determined in 73 and 23 men with prostate cancer and benign prostate hyperplasia (BPH), respectively, before treatment. There were no statistical differences of IL-11 levels between patients with prostate cancer and BPH. Patients with hormone-resistant prostate cancer had a significantly higher level of IL-11 than those with untreated cancer. Serum IL-11 levels may be a potential tumor marker for prostate cancer progression.