Circulating levels of interleukin-6 in patients with hormone refractory prostate cancer.

BACKGROUND: Interleukin-6 (IL-6) is a cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities. It is found in high levels in human ejaculate, and has recently been found to regulate prostate-specific protein expression in prostate cancer cells through nonsteroidal activation of the androgen receptor. IL-6 may be a candidate mediator of morbidity in patients with metastatic disease. We attempted to evaluate the potential of circulating IL-6 levels as a marker of disease progression. MATERIALS AND METHODS Serum IL-6, prostate specific antigen (PSA), percent free PSA (%fPSA), and prostate-specific membrane antigen (PSMA) were measured using commercially available assays in 407 men, including 15 controls. The rest of the study population had clinical or histologic evidence of prostate diseases, including 41 patients with chronic prostatitis, 167 with benign prostatic hyperplasia (BPH), 8 with high-grade prostatic intraepithelial neoplasia (PIN), 88 with localized prostate cancer, 22 with local recurrence after treatment of primary tumor, 4 with advanced untreated disease (nodal or bony metastases), 23 with advanced hormone dependent disease, and 39 with advanced hormone refractory disease (PSA > 1.0 ng/ml while on hormone treatment and/or evidence of disease progression). None had history of concurrent malignancy or acute inflammatory condition. Kruskal-Wallis analysis of variance and Spearman's correlation analysis were used for statistical analyses. RESULTS: Serum levels of IL-6 were significantly elevated in patients with clinically evident hormone refractory disease (5.7 +/- 1.9 pg/ml) and statistical significance was seen when comparing the elevated serum IL-6 levels to those in normal controls, prostatitis, BPH, and localized and recurrent disease, (P values < 0.01). Compared to serum levels of controls and BPH, PSA was significantly elevated in advanced untreated disease and hormone refractory groups (P < 0.05). Percent fPSA was significantly lower in all cancer patients but the hormone refractory. Serum PSMA was elevated in advanced untreated prostate cancer. Serum IL-6 showed positive correlation with PSMA and negative correlation with serum PSA but did not attain statistical significance. CONCLUSIONS: Serum IL-6 levels are significantly elevated in hormone-refractory prostate cancer patients and may be a surrogate marker of the androgen independent phenotype.     

Serum hepatocyte growth factor activator inhibitor type I (HAI-I) and type 2 (HAI-2) in prostate cancer

BACKGROUND: Hepatocyte growth factor activator inhibitor type 1 (HAI-1) and type 2 (HAI-2) are Kunitz-type serine protease inhibitors for hepatocyte growth factor activator (HGFA). We attempted to clarify whether serum levels of HAI-1 and HAI-2 could be a useful marker in patients with prostate cancer. METHODS: Serum levels of HAI-1 and HAI-2 were measured by enzyme-linked immunosorbent assay in 27 patients with benign prostatic hyperplasia (BPH) and 118 patients with prostate cancer. RESULTS: The mean serum levels of HAI-1 in patients with prostate cancer were significantly higher than those in patients with BPH. Furthermore, the serum HAI-1 levels in patients with distant metastasis and hormone resistant prostate cancer were significantly elevated compared with those in patients with organ-confined diseases. There were no significant differences in serum HAI-2 levels among prostate cancer subgroups according to clinical stage. Significantly elevated levels of HAI-1 were detected in 38 patients with prostate cancer before any treatment. CONCLUSIONS: HAI-1 may be a potential tumor marker for prostate cancer. Further studies in large groups of patients are needed to define the clinical value of HAI-1.     

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.     

Prostate specific antigen density for discriminating prostate cancer from benign prostatic hyperplasia in the gray zone of prostate-specific antigen.

Serum prostate specific antigen (PSA) is currently the best blood marker for prostate cancer. However, low specificity for detection of prostate cancer, especially in the gray zone of PSA, is a problem. We evaluated the clinical significance of PSA density (PSAD) in gray zone PSA cases with conversion of serum PSA to a Stanford reference value. In a series of histologically confirmed 63 benign prostatic hyperplasia (BPH) patients and 234 prostate cancer patients, 36 BPH patients and 25 prostate cancer patients had gray zone PSA levels. Serum PSA was measured with the Markit-F or Markit-M PA assay. All data were converted to Stanford reference values. We used transabdominal ultrasound to determine prostate volume. PSAD was determined as the serum PSA/prostate volume ratio. The mean PSA values for BPH and prostate cancer were 6.42 +/- 1.80 and 7.80 +/- 2.15 ng/ml (p = 0.0116), respectively, and prostate volume was 33.4 +/- 14.1 ml and 17.1 +/- 8.2 ml, respectively (p < 0.0001). The mean PSAD for prostate cancer was 0.572 +/- 0.363 while that for BPH was 0.218 +/- 0.085 (p = 0.0001). Cut-off values with sensitivity > 90% were 0.218 for PSAD and 30 ml for prostate volume. At these cut-off values, specificity reached 56% for each marker. In discriminating prostate cancer from BPH in the gray zone of PSA, PSAD demonstrated better performance than PSA.     

Immunoglobulin binding factor: A new tumor marker for prostatic tumors

Human seminal plasma contains an immunoglobulin gamma binding factor (IgBF) with an estimated molecular weight of 16 kD under reducing condition. IgBF was detected only in the prostate, including benign prostatic hypertrophy (BPH) and neoplasm. The present study was performed to determine whether IgBF is a useful prostatic marker. Serum IgBF levels were measured in patients with prostatic tumors and in control patients without tumor by radioimmunoassay. Serum prostatic-specific antigen (PSA), the standard prostatic marker, was also determined. Serum IgBF levels in patients with prostate cancer were significantly higher than those in age-matched controls (P < 0.05). Also, patients with BPH tended to have elevated IgBF levels than the controls, although the values were not statistically significant. In control patients, serum IgBF levels increased with advancing age. There was no correlation between serum levels of IgBF and PSA in patients with prostate cancer. Using cut-off level at 28.5 ng/ml (2 S.D. above the mean IgBF level of age-matched control), the sensitivities were 41.2% (7117) for prostate cancer, 23.1% (6/26) for BPH, and 5.6% (1/18) for control patients. In conclusion, serum IgBF is a useful marker in the diagnosis of patients with prostatic tumor, and in evaluating the course of treatment. © 1994 Wiley-Liss, Inc.     

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.     

Western blot assay for prostate-specific membrane antigen in serum of prostate cancer patients

There is a need for the development of new diagnostic tools for the early detection of prostate cancer. A candidate molecule for a new screening test is a prostate-specific membrane antigen (PSM) recognized by the monoclonal antibody 7E11.C5. We carried out studies aimed at identifying PSM in the serum of normal and benign prostatic hyperplasia (BPH) donors and patients with adenocarcinoma of the prostate, in order to judge whether the development of a serum assay using this marker was feasible. By Western blotting, we found significant levels of PSM in serum samples from prostatic cancer patients, in the seminal fluid of pooled normal donors, in BPH patients, and in normal male sera. Similar to prostate-specific antigen (PSA), PSM was present in seminal plasma in higher concentrations than in serum, and PSM levels in prostatic cancer patients were significantly higher than in normal controls. These data suggest that the development of an assay utilizing the PSM and new monoclonal antibodies directed against the antigen, could provide a feasible test for prostatic cancers. © 1994 Wiley-Liss, Inc.     

Serum insulin-like growth factor binding protein-3/prostate-specific antigen ratio is a useful predictive marker in patients with advanced prostate cancer

BACKGROUND: Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) play an important role in regulation of prostate cancer cell growth. We studied the prognostic significance of serum IGF-1 and IGFBP-3 levels, and IGF-1/prostate-specific antigen (PSA) and IGFBP-3/PSA ratios in patients with prostate cancer. METHODS: Serum levels of IGF-1, IGFBP-3, and PSA were determined in 112 patients diagnosed with prostate cancer. Serum samples from 32 patients with histologically confined benign prostatatic hyperplasia (BPH) served as control. RESULTS: Serum IGF-1 levels were significantly higher in advanced prostate cancer (n = 84) than in BPH patients (P < 0.01). IGFBP-3 levels were significantly lower in patients with advanced prostate cancer than in localized tumor (n = 28) or BPH (P < 0.05, each). Univariate analysis showed that serum PSA, IGF-1/PSA ratio, IGFBP-3/PSA ratio, T, N and M classifications correlated significantly with relapse-free survival of advanced prostate cancer patients treated with hormonal therapy. Multivariate analysis identified IGFBP-3/PSA ratio as the only significant variable for relapse-free survival (odds ratio 5.81, 95% CI 1.57-21.51). IGFBP-3/PSA ratio was also an independent predictor of cause-specific survival (stepwise analysis, odds ratio 4.86, P < 0.01). CONCLUSIONS: Our results suggested that IGFBP-3/PSA ratio might be a useful prognostic marker of advanced 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.     

前列腺癌骨转移患者血清中卵泡抑制素样蛋白1的表达及临床相关性研究

目的:探讨卵泡抑素样蛋白1(FSTL1)在前列腺癌骨转移患者中的表达,以及血清FSTL1与机体慢性炎性因子白介素6(IL-6)、细胞生长分化调节相关因子骨形成蛋白6(BMP6)的相关性,探讨血清FSTL1对前列腺癌骨转移的临床应用价值。方法:采用ELISA法测定35例前列腺癌骨转移患者和30例良性前列腺增生(BPH)患者血清FSTL1、IL-6、BMP6水平,并进行相关性分析。结果:前列腺癌骨转移组血清FSTL1的表达水平[(20.23±8.69)μg/L]较BPH组[(35.45±12.35)μg/L]明显降低(P0.01);血清IL-6、BMP6表达[(23.56±20.17)μg/L、(428.30±178.40)μg/L]较BPH组[(11.21±8.62)μg/L、(293.50±39.72)μg/L]明显增高(P0.05);前列腺癌骨转移组的血清FSTL1的表达与IL-6、BMP6呈显著负相关,相关系数分别为-0.971、-0.972(P0.05)。结论:前列腺癌骨转移患者血清FSTL1的表达降低,并且和体内炎症因子、细胞转化因子有关,为临床判断前列腺癌的发生及进展提供了新的生物学标记,为前列腺癌治疗提供了新的生物学靶向分子。     

Seminal plasma cytokines and chemokines in prostate inflammation: interleukin 8 as a predictive biomarker in chronic prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia

OBJECTIVE: This prospective study quantified cytokine and chemokine levels in seminal plasma of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH), to evaluate inflammatory mediators as possible surrogate markers for diagnosis and treatment efficacy. METHODS: Seminal plasma levels of eight cytokines and nine chemokines were evaluated by multiplex arrays in 83 men: 20 healthy controls and 9 men with CP/CPPS IIIA, 31 with CP/CPPS IIIB, and 23 with BPH. Prostate samples obtained by transurethral resection of the prostate from 13 patients with BPH were analysed by immunohistochemistry to detect interleukin 8 (IL-8)-producing cells and characterise inflammatory infiltrates. RESULTS: Significantly increased levels of cytokines (IL-1alpha, IL-1beta, IL-6, IL-10, IL12p70) and chemokines (CCL1, CCL3, CCL4, CCL17, CCL22, CXCL8/IL-8) were observed in seminal plasmas from patients with CP/CPPS or BPH. However, only IL-8 was significantly elevated compared to controls (median [quartiles] 1984 [1164-2444] pg/ml), in patients with CP/CPPS IIIA (15,240 [10,630-19,501] pg/ml; p<0.0001), CP/CPPS IIIB (2983 [2033-5287] pg/ml; p=0.008), and BPH (5044 [3063-11,795] pg/ml, p<0.0001), discriminating CP/CPPS IIIA versus IIIB (accuracy=0.882+/-0.078; p=0.001). Inflammatory infiltrates were detected in prostate samples from 13 of 13 BPH patients, and IL-8-producing prostate cells in 11 of 13 samples. IL-8 concentration in seminal plasma was positively correlated with symptom score and prostate-specific antigen levels both in CP/CPPS and BPH patients. CONCLUSIONS: IL-8 is expressed in situ by epithelial and stromal prostate cells and is functional, as shown by recruitment of cells expressing cognate receptors in BPH prostate tissue, indicating its involvement in disease pathogenesis. Among all the cytokines and chemokines analysed, IL-8 appears to be the most reliable and predictive surrogate marker to diagnose prostate inflammatory conditions, such as CP/CPPS and BPH.     

血清前列腺特异抗原测定的临床意义

以12例前列腺癌、102例前列腺良性增生(BPH)、16例直肠指检(DRE)异常、5例前列腺炎及30例正常男性为对象,用酶免法测定血清前列腺特异抗原(Prostate specific antigen,PSA)浓度,用放免法测定其中37例。前列腺癌的PSA浓度明显高于BPH(P<0.01),PSA对前列腺癌诊断的敏感性为91.7％。DRE异常者大于BPH(P<0.05),低于前列腺癌(P<0.01)。BPH高于正常对照(P<0.01)。前列腺切除术后一日的PSA高于术前(P<0.01),术后6～8日同术前无显著性差异(P>0.05)。70岁以上高于70岁以下(P<0.05)。PSA>10ng/ml时酶免检测值低于放免法(0.010.05)。单纯PSA升高并不能说明任何特异性病理过程,前列腺癌的诊断,应结合PSA系列测定值及DRE和经直肠B超(TRUS)来综合分析。     

Elevation of serum levels of urokinase-type plasminogen activator and its receptor is associated with disease progression and prognosis in patients with prostate cancer

BACKGROUND: Several investigators have revealed that urokinase-type plasminogen activator (uPA) and its receptor (uPAR) are overexpressed in serum as well as in tumor tissues in patients with various types of cancer. In this study, we examined whether the serum levels of uPA and uPAR could be used as predictors of the progression and prognosis of prostate cancer. METHODS: Serum levels of uPA and uPAR in 54 healthy controls, 62 patients with benign prostatic hypertrophy (BPH), and 72 patients with prostate cancer were measured by a sandwich enzyme immunoassay. RESULTS: The mean serum levels of uPA and uPAR in patients with prostate cancer were significantly higher than those in healthy controls and patients with BPH. Furthermore, the serum uPA and uPAR levels in prostate cancer patients with metastasis were significantly elevated compared with those in patients without metastasis. Among patients who underwent radical prostatectomy, the serum levels of uPA and uPAR in patients with pathologically organ-confined disease were significantly lower than in those with advanced disease. The overall survival rate of prostate cancer patients with elevated serum levels of either uPA or uPAR, or of both, was significantly lower than that of patients with normal serum levels of uPA and uPAR. CONCLUSIONS: The results of this study indicate that the elevation of serum levels of either uPA or uPAR, or of both, could be used as new predictors of progression and prognosis in patients with prostate cancer.     

BPH合并前列腺炎患者IPSS与IL-8、COX-2水平相关性研究

目的:观察良性前列腺增生(BPH)合并前列腺炎患者国际前列腺症状评分(IPSS)与前列腺按摩液(EPS)和前列腺组织中炎症因子白介素-8(IL-8)、环氧化酶-2(COX-2)水平的相关性。方法:将80例拟行经尿道前列腺电切术(TURP)BPH患者,根据术后病理学诊断分为单纯性增生组(30例)和增生伴炎症组(50例),两组均于术前行IPSS评分、EPS中IL-8、COX-2含量测定,术后前列腺组织中IL-8、COX-2的水平测定,进行统计学分析。结果:增生伴炎症组EPS中IL-8和COX-2水平显著高于单纯性增生组[IL-8:(15.31±1.22)ng/ml vs(5.89±0.91)ng/ml,COX-2:(371.09±14.99)ng/ml vs(156.96±29.47)ng/ml,P均<0.01],前列腺组织中两组IL-8和COX-2水平差异也显著(0.15±0.00 vs 0.05±0.02,0.13±0.01 vs 0.07±0.01,P均<0.01),IPSS两组差异也有显著性[(25.60±5.03)分vs(18.47±4.97)分,P<0.01];单纯增生组中IPSS与EPS和组织中IL-8及COX-2的表达呈中度相关(r=0.712、0.699、0.623、0.731,P均<0.05);增生伴炎症组中IPSS与IL-8、COX-2的表达呈高度相关(r=0.819、0.879、0.798、0.855,P均<0.05)。结论:EPS中IL-8、COX-2水平能间接反映前列腺组织中IL-8、COX-2水平,通过检测患者EPS中IL-8、COX-2水平并结合临床症状可以初步判定BPH患者是否合并前列腺组织学炎症。     

Osteopontin expression in prostate cancer and benign prostatic hyperplasia.

OBJECTIVES: Osteopontin (OPN), a secreted adhesive glycoprotein, has been shown to be produced in excessive amounts in a variety of experimental models of malignancy. Increased levels of OPN exist in blood from the lungs, breasts, and gastrointestinal tracts of cancer patients with metastases. However, there have been no reports on the expression of OPN in human urological malignancies. The present study investigates the presence of OPN in adenocarcinoma of the human prostate and in benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Using prostate tissue from 34 patients with primary prostate cancer, 13 patients with prostate cancer after having undergone hormonal therapy, and 12 patients with BPH, formalin-fixed paraffin sections were prepared. Specimens were obtained by needle biopsy or radical prostatectomy. Immunohistochemical staining (ABC method) was then performed. Staining was divided into either negative or positive categories. RESULTS: Positive staining of OPN was observed on cancer cells and macrophages in 52.9% of the primary prostate cancers and 14.5% of the prostate cancers after hormonal therapy. In BPH specimens, 66.7% of the cases displayed positive staining of OPN. The staining level of OPN showed no correlation with serum prostate-specific antigen, but did correlate with stage, differentiation, and Gleason's score. CONCLUSIONS: The result postulates that the expression of OPN is an indicator of cell differentiation; however, it cannot be used as a marker of malignancy in prostate cancer.     

游离PSA与总PSA比值在前列腺癌鉴别诊断中的意义

目的　探讨游离前列腺特异性抗原 (fPSA)与总前列腺特异性抗原 (tPSA)比值 (f tPSA)在tPSA为 4～ 10ng ml时对前列腺癌和良性前列腺增生 (BPH)鉴别的意义及其局限性。方法　对1998年 10月至 2 0 0 2年 10月接受诊治的 180例血清tPSA为 4～ 10ng ml的前列腺癌和BPH患者进行回顾性分析。经组织学证实 ,36例 (2 0 % )是前列腺癌 ,14 4例 (80 % )是BPH。血清中tPSA和fPSA通过酶免微粒子捕捉法测定。前列腺体积通过经腹壁超声测定。前列腺癌与BPH组间比较用t检验。采用Pearson相关系数分析前列腺体积与f tPSA之间的相关性。结果　前列腺癌患者的tPSA、f tPSA平均值分别是 6 75ng ml与 0 17;BPH患者则是 6 4 8ng ml和 0 2 5。两组患者的tPSA差异无显著意义 (P >0 0 5 ) ,而前列腺癌患者的f tPSA值显著低于BPH患者 (P <0 0 1)。此外 ,两组患者的前列腺体积与f tPSA均呈显著正相关 (前列腺癌组相关系数r=0 5 0 ,P <0 0 1;BPH组r=0 2 4 ,P <0 0 1)。在前列腺体积小于 4 0cm3,两组患者的f tPSA差异有显著意义 (P <0 0 5 ) ,当体积超过 4 0cm3,则差异无显著意义 (P >0 0 5 )。结论　f tPSA对tPSA在 4～ 10ng ml之间的前列腺癌和BPH的鉴别诊断有重要意义 ,但由于受前列腺体积的影响 ,只有在     

Serum osteoprotegerin (OPG) levels are associated with disease progression and response to androgen ablation in patients with prostate cancer

BACKGROUND: Osteoprotegerin (OPG) is a tumour and/or bone derived factor that may protect tumour cells from apoptosis. In this study, we have measured serum OPG levels in untreated prostate cancer patients with advanced prostate cancer compared to patients with organ confined disease and in treated patients receiving androgen ablation. METHODS: Serum OPG levels were measured by ELISA in samples collected from 104 patients with either newly diagnosed (n = 59) or advanced prostate cancer treated by androgen ablation (n = 45) and compared with levels in serum from patients with benign prostatic hyperplasia (BPH) (n = 10) and young healthy men (n = 10). RESULTS: Untreated patients with locally advanced disease had significantly higher OPG levels than those with organ confined disease. Patients with advanced disease responding to androgen ablation (serum PSA < 1 ng/ml) had serum OPG levels that were significantly lower than those with clinically progressing disease (PSA > 10 ng/ml). OPG levels in the latter were not significantly different from levels in patients with early signs of biochemical progression (PSA >1 but <10 ng/ml). CONCLUSIONS: OPG is a potential new marker, which is elevated in the serum of patients with advanced prostate cancer and may be an indicator of early disease progression.     

前列腺癌患者血清前梯度蛋白2的水平及其临床意义

目的 通过检测前列腺癌患者血清前梯度蛋白2(AGR2)的水平,探讨其在前列腺癌患者中的临床应用价值.方法 收集前列腺癌患者治疗前后血液标本46例,良性前列腺增生(BPH)患者血液标本20例,健康对照组血液标本20例,用酶联免疫吸附测定法检测三组血清AGR2水平.分析血清AGR2与前列腺癌病理分级及临床分期的关系.结果 ①前列腺癌组患者治疗前血清AGR2水平均明显高于BPH组和健康对照组(P＜0.01),BPH组和健康对照组之间差异无统计学意义(P＞0.05);②前列腺癌组患者治疗后血清AGR2较治疗前明显降低(P＜0.01),行前列腺癌手术患者术前血清AGR2水平明显高于术后(P＜0.01),行内分泌治疗的前列腺癌患者治疗前AGR2水平明显高于治疗后(P＜0.01);③治疗前血清AGR2水平与前列腺癌临床分期、Gleason病理分级明显相关(P＜0.05),血清AGR2水平与PSA水平显著相关(P＜0.01);④ROC曲线下面积0.792(95％CI:0.698 ～ 0.886),当临界值为13.75 ng/mL,灵敏度71.7％,特异度75.0％.结论 前列腺癌患者血清AGR2水平增高,与临床分期及Gleason病理分级有关,提示AGR2在前列腺癌诊断、恶性程度以及疗效判断具有一定的临床意义.     

前列腺特异性抗原升高的组织病理学基础

目的 探讨前列腺特异性抗原(PSA)与前列腺结节增生、Ⅳ型前列腺炎及前列腺癌之间的关系,探讨PSA升高的病理学基础.方法 有完整临床病理资料的前列腺疾病504例患者,均无前列腺癌和穿刺活检史,均行PSA、全身骨扫描、MRI和前列腺穿刺活检.直肠B超引导下以18G自动穿刺活检枪行双侧叶6-13点法前列腺穿刺活检.对患者穿刺的病理标本按前列腺结节增生、前列腺癌以及Ⅳ型前列腺炎病理诊断标准进行评价.结果 504例患者经病理证实前列腺癌185例(37%),Ⅳ型前列腺炎109例(21%),前列腺增生210例(42%).3组总PSA(t-PSA)分别为27.6(0.4～7116)、10.6(0.2～168)和9.2(0.3～60)ng/ml,3组间比较差异有统计学意义(P＜0.01);f-PSA分别为3.5(0.1～3356)、1.7(0.1～42)和1.5(0.06～15.8)ng/ml,3组间比较差异有统计学意义(P＜0.001);f/t-PSA分别为0.14(0＜0.94)、0.17(0.04～0.91)和0.16(0.02～0.75).3组间比较差异有统计学意义(P=0.019);3组间年龄、B超、直肠指诊结果比较差异无统计学意义(P＞0.05).前列腺癌分级与f-PSA(r=0.33,P＜0.001)、t-PSA(r=0.27,P＜0.001),f/t-PSA(r=0.22,P=0.003)具有显著相关性;多元线性回归分析发现前列腺癌分级与f-PSA(t=-2.34,P=0.02),t-PSA(t=2.77,P=0.006),f/t-PSA(t=3.97,P＜0.001)具有显著相关性.前列腺癌临床分期间f-PSA和t-PSA差异有统计学意义(P＜0.001).210例前列腺增生患者若按腺体增生为主和间质增生为主2类比较,t-PSA和f-PSA差异均有统计学意义(P＜0.05).多元线性回归分析发现t-PSA足前列腺增生病理结节类型最相关的指标,t-PSA≥2.5 ng/ml,确定腺体增生为主型前列腺增生的敏感性为96%,特异性为20%(P＜0.05).Ⅳ型前列腺炎109例和前列腺增生210例,2组间比较f-PSA,t-PSA,f/t-PSA差异有统计学意义(P＜0.05).通过ROC曲线确定前列腺癌敏感指标的界值:f-PSA≥0.85 ng/ml,t-PSA≥4 ng/ml和f/t-PSA≤0.16(P＜0.05).结论 血清PSA升高的病理基础为任何破坏前列腺上皮血屏障的病变;任何形成前列腺上皮增生,分泌更多PSA的病变;其中以破坏前列腺上皮血屏障最重要.     

Hormonal predictors of prostate cancer

INTRODUCTION: Androgens are necessary for the development and functioning of the prostate gland. The association of serum testosterone and pituitary hormone levels with prostate cancer development is not completely understood. In this clinical study, we evaluated the role of serum testosterone, free testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in predicting prostate cancer risk in patients who had transrectal ultrasonography-guided prostate biopsy with the suspicion of prostate cancer. MATERIAL AND METHODS: A total of 211 patients who were selected to undergo prostatic biopsy due to abnormal digital rectal examination and/or a serum prostate-specific antigen (PSA) level >2.5 ng/ml were included in the study. The patient characteristics of total PSA, free/total PSA ratio, serum total testosterone, free testosterone, free/total testosterone ratio, FSH and LH levels were compared according to the pathological diagnosis. RESULTS: The mean age was 63.91 years (range 44-83) and the mean PSA level was 9.23 ng/ml (range 0.13-50.41) in the whole group. Of 211 patients, 69 (32.7%) were positive for prostate cancer. The patients who were positive for prostate cancer had statistically lower levels of serum total testosterone compared with the patients who were diagnosed as having benign prostatic hyperplasia (BPH; 405 vs. 450.5 ng/dl, respectively; p = 0.013). The serum FSH level was significantly higher in men with prostatic cancer than in men with BPH (7.56 vs. 6.06 mIU/ml, respectively; p = 0.029). No significant differences between men with prostatic cancer and those with BPH were found for serum LH levels. When normal ranges for serum free and total testosterone levels were defined as 9 pg/ml and 300 ng/dl, respectively, patients who had low free testosterone and total testosterone levels had significantly higher cancer detection rates than patients with high serum androgen levels: 40.8% (40/98) versus 25.6% (29/113) (p = 0.021), and 48.6% (18/37) versus 29.3% (51/174), respectively (p = 0.023). After logistic regression analysis, none of the hormones showed a significant difference in predicting the risk of prostate cancer in patients undergoing prostate biopsy with suspicion of the disease. CONCLUSION: Our data suggest that patients diagnosed with prostate cancer have low levels of serum testosterone and high levels of serum FSH compared with the patients with BPH. No support was found for the theory that high levels of testosterone increase prostate cancer risk. Further studies are needed to clarify the relationship between hormones and prostate cancer etiology.