Clinical significance of the leptin and leptin receptor expressions in prostate tissues

Aim： To evaluate the expression of leptin and leptin receptor in benign prostatic hyperplasia （BPH） and prostate cancer （PCa）, and to investigate whether they are associated with the development and progression of PCa. Methods： hnmunohistochemical staining was performed to examine the expression of leptin and leptin receptor in BPH and PCa. PCa was divided into three groups： localized PCa, locally advanced PCa and metastatic PCa. The positive staining was identified and the percentage of the positive staining was graded. We also assessed the relationship between both the Gleason score and body mass index （BMI） and PCa. Results： The percentage of the leptin expression in PCa was significantly higher than that in BPH （P 〈 0.01）. For the PCa group, the expressed levels of leptin showed a considerable correlation with localized PCa and metastatic PCa （P 〈 0.05）. Leptin receptor, however, did not reveal a definite difference between BPH and PCa. The expression of leptin indicated a significant difference between well-differentiated PCa （Gleason score ≤6） and poorly differentiated PCa （Gleason score 8-10） （P 〈 0.05）. The relation between the leptin expression level in PCa and the BMI was not remarkable （P = 0.447）. Conclusion： Our results suggest that leptin might have a promoting effect on the carcinogenesis and progression of PCa.     

Prostate cancer antigen-1 as a potential novel marker for prostate cancer

Aim： To examine the expression of prostate cancer antigen-1 （PCA-1） in prostate cancer （PCa） and to validate it as a potential marker for diagnosis of PCa. Methods： In situ hybridization analysis of PCA-1 mRNA expression was performed on 40 benign prostate hyperplasia （BPH）, 16 high-grade prostatic intraepithelial neoplasm （HG-PIN）, 74 PCa and 34 other malignant carcinoma specimens. The level of PCA- 1 expression was semiquanfitatively scored by assessing both the percentage and intensity of PCA- 1 positive staining cells in the specimens. We then compared the PCA-1 expression between BPH, HG-PIN and PCa and evaluated the correlation of PCA-1 expression level with clinical parameters of PCa. Results： PCA-1 mRNA was expressed in the majority of both PCa and HG-PIN specimens but not in BPH and other malignant carcinoma. The expression level of PCA-1 increased along with a high Gleason score （P 〈 0.05）, and was unrelated to other clinical parameters of PCa （all P 〉 0.05）. Conclusion： The data suggest that PCA-1 might be a novel diagnostic marker for PCa, and that increased PCA-1 expression might denote more aggressive variants of PCa.     

Prostate calculi in cancer and BPH in a cohort of Korean men：presence of calculi did not correlate with cancer risk

Prostatic calculi are common and are associated with inflammation of the prostate. Recently,it has been suggested that this inflammation may be associated with prostate carcinogenesis. The aim of this study was to investigate the relationship between prostatic calculi and prostate cancer （PCa） in prostate biopsy specimens. We retrospectively analyzed 417 consecutive patients who underwent transrectal ultrasonography （TRUS） and prostate biopsies between January 2005 and January 2008. Based on the biopsy findings,patients were divided into benign prostatic hyperplasia and PCa groups. TRUS was used to detect prostatic calculi and to measure prostate volume.The correlations between PCa risk and age,serum total PSA levels,prostate volume,and prostatic calculi were analyzed. Patient age and PSA,as well as the frequency of prostatic calculi in the biopsy specimens,differed significantly between both the groups （P〈0.05）. In the PCa group,the Gleason scores （GSs） were higher in patients with prostatic calculi than in patients without prostatic calculi （P = 0.023）. Using multivariate logistic regression analysis,we found that patient age,serum total PSA and prostate volume were risk factors for PCa （P = 0.001）,but that the presence of prostatic calculi was not associated with an increased risk of PCa （P = 0.13）. In conclusion,although the presence of prostatic calculi was not shown to be a risk factor for PCa,prostatic calculi were more common in patients with PCa and were associated with a higher GS among these men.     

VEGF和VEGF-C表达增加与前列腺癌进展的相关性研究

目的探讨前列腺癌(PCa)组织及癌周正常组织中血管内皮细胞生长因子(VEGF)、血管内皮细胞生长因子C(VEGF-C)表达与PCa进展的相关性。方法采用SABC免疫组化染色法对71例PCa组织标本中CD34、VEGF及VEGF-C的表达进行检测,并对所获得的数据进行统计分析。结果与癌周正常组织相比,PCa上皮/肿瘤细胞内VEGF和VEGF-C表达显著上调(P<0.01)。Jewett-Whitmore分期D期癌灶内VEGF-C表达显著高于A、B或C期患者(P<0.01)。Jewett-Whitmore分期与VEGF-C(rs=0.738,P<0.001)、MVD与VEGF(rs=0.492,P<0.001)之间存在显著的相关性。结论VEGF和VEGF-C表达增加与PCa的进展密切相关。VEGF促进肿瘤组织内部微血管形成,而VEGF-C的主要作用在于促进淋巴管形成。     

Genetic variations of the ADIPOQ gene and risk of prostate cancer in Chinese Han men

Adiponectin secreted by adipose tissue has been implicated in prostate carcinogenesis. Genetic variations in ADIPOQare thought to influence the activity of adiponectin, thus relating to cancer occurrence. In this hospital-based case-control study of 917 prostate cancer （PCa） cases and 1036 cancer-free controls, we evaluated the association of single nucleotide polymorphisms in ADIPOQ with risk of PCa and adiponectin levels in Chinese Han men. Variants of ADIPOQ were genotyped by Taqman polymerase chain reaction method. The plasma adiponectin concentrations were measured by enzyme.linked immunosorbent assay （ELISA） in a subset of cases and controls. We found that the ADIPOQ rs3774262 variant AA genotype was associated with both decreased PCa risk [adjusted odds ratio （OR）： 0.66, 95% confidence interval （CI） =0.48-0.92] and increased plasma adiponectin levels （P= 0.036 and 0,043）, with significant difference by tumor grade, clinical stage, and aggressiveness. A significant interaction between ADIPOQ rs3774262 and body mass index was observed in modifying the risk of PCa （P=6.7 × 10-3）. ADIPOQ rs266729 and rs182052 were not related to PCa risk or plasma adiponectin levels. Our data support that ADIPOQ rs3774262 may affect PCa risk in combination with plasma adiponectin levels in Chinese Han men. It may contribute to the molecular basis for the association between obesity and PCa.     

合并前列腺炎的前列腺增生组织中COX-2、VEGF的表达

Objectives To study the expressions of Vascular endothelial growth factor ( VEGF) and cyclooxygenase-2 in benign prostatic hyperplasia combined with Prostatitis,analyze their correlation and to investigate the effect and molecular mechanism of prostatitis on BPH.Methods 60 specimens were obtained from patients undergoing transurethral prostatic resection(TURP).The paraffin section of the specimens were stained with hematoxylin and eosin,and observed under light microscope to examine the inflammation pathological changes.Depending on whether the benign prostatic hyperplasia combined with prostatitis,those specimens were divided into group of simple benign prostatic hyperplasia ( A group) and group of benign prostatic hyperplasia combined with prostatitis ( B group),using inununohistochemistry and Real-time fluorescence quantitative PCR ( RT-PCR) to detect the expressions of COX-2 and VEGF in prostate tissues.Results (1) immunohistochemical staining: COX-2 and VEGF expressed in the A group and B group,but in the B group of tissues were significantly higher than A group of tissues( p <0.05); COX-2 and VEGF expression in the B group of organizations had a positive correlation ( R = 0.92,p <0.05) (2) COX-2 mRNA in the A group,the relative ratio; 0.141 ± 0.019,in the B group,the relative ratio: 0.161 ± 0.013;VEGF mRNA in the A group relative ratio: 0.2S4 ± 0.015,in the B group,the relative ratio; 0.341 ± 0.012,The expressions of COX-2mRNA and VEGF mRNA in the B group were significantly higher than the expressions of A group ( p <0.05) .Conclusions The inflammatory factor COX-2 and proliferative factor VEGF in the tissues of benign prostatic hyperplasia combined with prostatitis are significantly increased and the expression levels of both positive correlation,COX-2 by the way of up-regulating VEGF expression may be involved in the development process of benign prostatic hyperplasia.     

合并前列腺炎的前列腺增生组织中COX-2、VEGF的表达

Objectives To study the expressions of Vascular endothelial growth factor ( VEGF) and cyclooxygenase-2 in benign prostatic hyperplasia combined with Prostatitis,analyze their correlation and to investigate the effect and molecular mechanism of prostatitis on BPH.Methods 60 specimens were obtained from patients undergoing transurethral prostatic resection(TURP).The paraffin section of the specimens were stained with hematoxylin and eosin,and observed under light microscope to examine the inflammation pathological changes.Depending on whether the benign prostatic hyperplasia combined with prostatitis,those specimens were divided into group of simple benign prostatic hyperplasia ( A group) and group of benign prostatic hyperplasia combined with prostatitis ( B group),using inununohistochemistry and Real-time fluorescence quantitative PCR ( RT-PCR) to detect the expressions of COX-2 and VEGF in prostate tissues.Results (1) immunohistochemical staining: COX-2 and VEGF expressed in the A group and B group,but in the B group of tissues were significantly higher than A group of tissues( p <0.05); COX-2 and VEGF expression in the B group of organizations had a positive correlation ( R = 0.92,p <0.05) (2) COX-2 mRNA in the A group,the relative ratio; 0.141 ± 0.019,in the B group,the relative ratio: 0.161 ± 0.013;VEGF mRNA in the A group relative ratio: 0.2S4 ± 0.015,in the B group,the relative ratio; 0.341 ± 0.012,The expressions of COX-2mRNA and VEGF mRNA in the B group were significantly higher than the expressions of A group ( p <0.05) .Conclusions The inflammatory factor COX-2 and proliferative factor VEGF in the tissues of benign prostatic hyperplasia combined with prostatitis are significantly increased and the expression levels of both positive correlation,COX-2 by the way of up-regulating VEGF expression may be involved in the development process of benign prostatic hyperplasia.     

CD44s和CD15在前列腺癌组织中的表达及其意义

Objectives To investigate expression of cell adhesion molecule CD44 sand CD15 in prostate carcinoma(PCa), and to evaluate its clinical significance. Methods Forty two cases of PCa and 15 of benign prostate hyperplasia(BPH) were detected by immunolhistochemical technique and the intensity of CD44s and CD15 expression was assessed by computer image analysis system. Results (1) The intensity of CD44s expression was significantly lower in PCa than that in BPH. PCa showed significant loss of CD44s expression, which correlated with the rise of tumor Gleason grade and clinical stage( p＜0.01 ), The intensity of CD44s expression was significantly lower inmetastasis group than that in nonmetastasis group( p ＜ 0.01 ). (2)The intensity of CD15 expression was significantly higher in PCa than that in BPH. The upregnlation of the CD15 correlated with the rise of tumor Gleason grade and clinical stage( p＜0.01 ). The intensity of CD15 expression was significantly higher in metastasis group than in nonmetastasis group. (3)There was significant reverse correlation between the expression level of CD44s and CD15 (r = -0.785, p＜0.001). Conclusions Aberrant expressions of CD44s and CD15 may be correlated with clinical stage, Gleason grade and metastasis in PCa. CD44s and CD15 play an important role in the malignant progression of PCa, and could be used as a marker of malignant potention and prognosis of patient with PCa.     

Heat shock and other apoptosis-related proteins as therapeutic targets in prostate cancer

Defects within apoptotic pathways have been implicated in prostate cancer （PCa） tumorigenesis, metastatic progression and treatment resistance. A hallmark of cancers is the ability to derail apoptosis by inhibiting the apoptotic signal, reducing the expression of apoptotic proteins and/or amplifying survival signals through increased production of antiapoptotic molecule. This review describes associations between heat shock proteins （HSPs） and the human androgen receptor （AR）, the role of HSPs and other stress-induced proteins in PCa development and emerging strategies in targeting these protective proteins to treat PCa.     

Expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in human prostate

BACKGROUND: The growth and dissemination of tumors has been associated with angiogenesis, which is regulated by a group of polypeptide factors including vascular endothelial growth factor-C (VEGF-C). VEGF-C binds its receptor, vascular endothelial growth factor receptor-3 (VEGFR-3) to promote growth of tumor-associated lymphatic vessels. METHODS: In this study, microarray technology was used to build tissue arrays of normal prostate, benign prostate hyperplasia (BPH) and prostate carcinomas (PCa) using tissues from 640 patients. Slides were sectioned and stained with a polyclonal antibody to VEGFR-3 using a standard immunoperoxidase method and digitized. Immunoreactivity was scored using a 0-3+ semiquantitation scoring system for both intensity and percentage. The sum index was obtained by totaling the scores. RESULTS: VEGFR-3 is expressed in normal prostate, BPH, and PCa, but VEGFR-3 expression is up-regulated in PCa. We also found that VEGFR-3 is correlated with pre-operative prostate-specific antigen (Pre-PSA), Gleason score, and lymph node metastasis. The recurrence-free 5-year survival in cases with lower sum index (0-3) was significantly higher than that in cases with higher sum index (4-6) (77.3, 69.6%, respectively, P = 0.037) by Kaplan-Meier actuarial model. CONCLUSIONS: Our data suggest that VEGFR-3 expression is associated with tumor progression and may play an important role in facilitating lymphatic spread of PCa; high-level of VEGFR-3 expression in prostate cancer cells increases the risk of biochemical recurrence in prostate cancer patients treated by radical prostatectomy.     

肾上腺皮质癌中类肝素酶-1和血管内皮生长因子的表达及其与微血管密度的关系

目的探讨类肝素酶-1（Heparanase-1,HPA-1）、血管内皮生长因子（vascular endothelial growth factor,VEGF）和血管内皮生长因子受体2（vascular endothelial growth factor receptor-2,VEGFR-2）在肾上腺皮质癌（adrenocortical carcinoma,ACC）中的表达及HPA-1和VEGF两者与微血管密度（microvessel density,MVD）的关系。方法采用免疫组化技术,检测20例肾上腺皮质腺瘤和24例肾上腺皮质癌组织中HPA-1、VEGFR-2、VEGF和MVD的表达情况。站果HPA-1在ACC组中的表达为91．67％（22／24）,良性组中为15．OO％（3／20）,ACC组与良性组之间HPA-1的表达有极显著性差异（P〈0．01）;VEGF在ACC组中呈高表达（17／24,70．83%）,在良性组中表达较低（5／20,25．00％）,ACC组与良性组之间VEGF的表达有显著性差异（P〈0．05）;VEGFR-2在ACC组中呈高表达（19／24,79．17％）,在良性组中表达较低（5／20,25．00％）,两者之间有显著性差异（P〈0．05）;MVD在ACC组中的表达为（84．70±12．44）,显著高于良性组（21．05±8．07）,差异具有统计学意义（P〈0．05）。结论HPA-1、VEGFR-2和VEGF在ACC组织中的高表达及HPA-1、VEGF的表达与MVD间呈正相关,为抗肿瘤血管生成治疗在ACC中的应用提供了相应的理论依据。     

VEGF、VEGFR-2和MVD在肾上腺皮质癌中的表达及意义

目的探讨VEGFR-2、VEGF和MVD在肾上腺皮质癌(ACC)中的表达及其临床意义。方法选取经手术治疗且具有完整的临床、病理资料的肾上腺皮质肿瘤存档石蜡标本37例,其中良性组20例,恶性组(ACC组)17例。采用免疫组化技术,检测良、恶性肾上腺皮质肿瘤中VEGFR-2、VEGF和MVD的表达情况。结果 VEGFR-2在ACC组中呈高表达(76.47%),在良性组中表达较低(25.00%),ACC组与良性组之间VEGFR-2的表达有显著性差异(P0.05)。VEGF在ACC组中呈高表达(70.59%),在良性组中表达较低(25.00%),VEGF在ACC组中的表达与在良性组中的表达有显著性差异(P0.05)。MVD在ACC组中的表达为(76.40±15.64),良性组中为(21.05±8.07),两者之间有显著性差异(P0.05)。结论 VEGFR-2和VEGF以及MVD在ACC中的高表达为抗肿瘤血管生成治疗在ACC中的应用,提供了一定的理论依据。     

低氧诱导因子1α及血管内皮生长因子在前列腺癌中的表达及意义

目的:观察低氧诱导因子1α(H IF-1α)及血管内皮生长因子(VEGF)在前列腺癌(PCa)中的表达及意义。方法:32例PCa患者,根据G leason评分,将≥7分者设为高G leason评分组(n=12),<7分者为低G leason评分组(n=20)。良性前列腺增生(BPH)16例,BPH伴高级别前列腺上皮内瘤(PIN)15例,正常前列腺组织(NP)12例。采用免疫组化染色CD34观察各组组织中微血管密度(MVD)及H IF-1α、VEGF的表达情况。结果:PCa、PIN中H IF-1α阳性表达率分别为62.5%、60.0%,较BPH(6.3%)及NP(0)高,差异有统计学意义(P<0.05)。PCa、PIN中VEGF阳性表达率分别为78.1%、73.3%,较BPH(18.7%)及NP(8.3%)高,差异亦有统计学意义(P<0.05)。PCa的MVD为66.9±18.0,明显高于BPH(28.3±6.9)及NP(15.3±2.9)(P<0.05)。高G leason评分组H IF-1α、VEGF阳性率及MVD值均高于低G leason评分组,差异均有显著性(P<0.05)。结论:H IF-1α及VEGF过表达是PCa形成的早期事件,与PCa密切相关。     

前列腺癌组织中血管内皮生长因子的表达及其与内皮素-1的相关性研究

目的:探讨血管内皮生长因子(VEGF)在BPH及PCa中的表达和临床意义,及其与内皮素-1(ET-1)表达的关系。方法:应用免疫组织化学ElivisionTMplus法对44例前列腺癌和36例前列腺增生组织中VEGF和ET-1分别进行免疫组化染色,并在光镜下判断染色部位和染色强度。结果:VEGF在BPH和PCa组织中阳性表达率分别为69.4%和80.9%;阳染部位主要位于肿瘤和增生的腺上皮细胞,间质血管内皮细胞均强阳性;比较BPH和PCa的VEGF表达强度,两者有显著性差异(P<0.05);低分化PCa的ET-1表达强度显著高于中、低分化PCa(P<0.01);在骨转移(BM)PCa中VEGF表达强度显著高于非骨转移(non-BM)癌(P<0.01)。VEGF与ET-1的表达有显著的正相关性(rs=0.780,P<0.01)。结论:VEGF与PCa的发生发展有关,其过度表达可能在PCa的骨转移中起重要作用。VEGF与ET-1可能共同参与了PCa的发生发展。     

端粒酶逆转录酶与血管内皮细胞生长因子在前列腺癌中的表达及其相关性的研究

目的:探讨端粒酶逆转录酶(TRT)、血管内皮细胞生长因子(VEGF)在前列腺癌(PCa)中的表达及两者的相关性。方法:应用免疫组化染色(SP)法结合计算机辅助图像分析方法,对30例病理证实为PCa和30例良性前列腺增生(BPH)穿刺标本中的TRT、VEGF的表达进行半定量分析。结果:30例PCa标本中,TRT、VEGF阳性表达率分别是63.3%(19/30)和76.7%(23/30);30例BPH标本中,TRT、VEGF阳性表达率分别是16.7%(5/30)和46.7%(14/30),组间差异均有显著性意义(P<0.05)。TRT与VEGF的表达显著相关(r=0.833 3,P<0.05)。结论:TRT、VEGF的表达可能是PCa的恶性表型,两者的表达具有显著相关性,但其确切机制还需深入研究。     

胃癌组织中hTERT和VEGF表达与微血管密度的关系及其临床意义

目的：探讨胃癌组织中人端粒酶逆转录酶（hTERT）、血管内皮生长因子（VEGF）表达与微血管密度（MVD）的相关性及其临床意义。方法：采用超敏SP法检测138例胃癌的hTERT、VEGF表达和肿瘤MVD,结合临床病理学特征进行相关分析。结果：本组胃癌组织hTERT表达阳性率为81．2％（112／138）,VEGF表达阳性率为85．5％f118／1381,MVD平均为45．8。hTERT阳性表达与胃癌的浸润深度、淋巴结状态、临床分期具有相关性,VEGF阳性表达与组织学分化型、淋巴结转移、血管浸润相关,MVD与浸润深度、淋巴结状态相关;VEGF表达与MVD值存在显著性意义。结论：hTERT激活与VEGF表型在胃癌进程中发挥重要作用,检测hTERT、VEGF表达和MVD,对胃癌诊断和预后的判断具有一定的价值。     

血管内皮生长因子、血小板反应素1在肾上腺皮质肿瘤中的表达及其意义

目的讨论血管内皮生长因子（VEGF）与血小板反应素1（TSP-1）在肾上腺皮质肿瘤中的表达及其临床意义。方法选取经手术治疗且取得完整临床资料的肾上腺皮质肿瘤石蜡包埋标本37例,其中良性组20例,恶性组（ACC组）17例。采用免疫组化技术,检测并分析良、恶性肾上腺皮质肿瘤中VEGF和TSP-1的表达情况。结果TSP-1在ACC组中呈低表达（5／17,29．41％）,在良性组中表达高（13／20,65．00％）,ACC组与良性组之间TSP-1的表达有显著性差异（P〈0．05）。VEGF在ACC组中呈高表达（70．59％）,在良性组中表达较低（25．00％）,VEGF在ACC组中的表达与在良性组中的表达有显著性差异（P〈0．05）。微血管密度（MVD）在ACC组中的表达为（76．40±15．64）／视野,良性组中为（21．05±8．07）／视野,两者之间有显著性差异（P〈0．05）。VEGF的表达和MVD呈正相关（P〈0．01）,TSP-1的表达和MVD呈负相关（P〈0．01）。VEGF的表达和TSP-1的表达呈负相关（rs＇=-0．386）。结论VEGF与TSP-1表达不平衡可能是肾上腺皮质肿瘤肿瘤性血管生成的重要原因,有望为抗肿瘤靶向治疗在ACC中的应用提供相应的理论依据。