Annexin Ⅰ蛋白在人前列腺癌中的表达及临床意义

目的:探讨Annexin Ⅰ蛋白在前列腺癌组织中的表达及其与前列腺癌发生、发展、转移及预后的关系.方法:回顾性分析110例前列腺癌及40例前列腺增生组织中Annexin Ⅰ蛋白的表达与前列腺癌Gleason分级、年龄、临床分期、转移及预后的相关性.结果:前列腺癌患者的Armexin Ⅰ表达水平显著地低于良性前列腺增生症患者(P＜0.05);Annexin Ⅰ在低分化癌中表达较高,与高、中分化癌相比有显著性差异(P＜0.05);而高、中分化癌之间Annexin Ⅰ表达均较低,两者之间无显著性差异(P＞0.05).前列腺癌Annexin Ⅰ蛋白表达与年龄无关,而与临床分期、淋巴结转移及预后有关(P＜0.05).结论:Annexin Ⅰ蛋白表达下调与前列腺癌发生发展和预后密切相关,可作为反映前列腺癌生物学行为和判断预后的生物标记物.     

CD147 在前列腺癌中的表达及其与肿瘤临床病理特征的关系

目的:研究CD147在还没前列腺癌组织中的表达及其与肿瘤临床病理特征的关系。方法:选择2013年10月-2015年10月我院收治的前列腺癌患者61例作为研究对象,另选取同期接受手术治疗的前列腺增生患者49例作为对照组,术中收集前列腺癌患者的肿瘤组织和癌旁组织以及前列腺增生患者的组织标本,采用免疫组化法检测CD147在前列腺癌组织、癌旁组织及前列腺增生组织中的表达情况。结果:CD147在前列腺癌组织中的阳性表达率(95.08%)显著高于癌旁组织(32.79%)和前列腺增生组织(16.32%),差异具有统计学意义(P0.05);CD147在癌旁组织中的阳性表达率(32.79%)高于前列腺增生组织(16.32%),差异具有统计学意义(P0.05)。CD147的阳性表达与前列腺癌Gleason分级、临床分期、淋巴结转移及远处转移呈正相关关系(P0.05)。结论:CD147在前列腺癌组织中呈阳性表达,且Gleason病理分级≥5、临床分期T3~4、淋巴结转移N1及远处转移M1均为前列腺癌组织中CD147m RNA阳性表达的危险因素。     

PTEN蛋白表达与前列腺癌病理分期的关系

目的:探讨PTEN蛋白在前列腺癌组织中的表达及其临床意义。方法:应用免疫组织化学S-P方法,检测前列腺癌及良性前列腺增生组织中PTEN蛋白的表达。结果:PTEN蛋白表达阳性随肿瘤细胞病理分级、临床分期的增高,PTEN蛋白阳性表达率降低。结论:PTEN蛋白异常表达在前列腺癌的进展中有重要作用,检测PTEN蛋白的表达有助于判断病情及预后。     

PTEN蛋白表达与前列腺癌病理分期的关系

目的：探讨PTEN蛋白在前列腺癌组织中的表达及其临床意义。方法：应用免疫组织化学S-P方法,检测前列腺癌及良性前列腺增生组织中PTEN蛋白的表达。结果：PTEN蛋白表达阳性随肿瘤细胞病理分级、临床分期的增高,PTEN蛋白阳性表达率降低。结论：PTEN蛋白异常表达在前列腺癌的进展中有重要作用,检测PTEN蛋白的表达有助于判断病情及预后。     

Cox-2、P504s、CK3413E12和P63在前列腺腺癌中的表达及其临床意义

目的:研究Cox-2、P504s、CK34βE12和P63在前列腺腺癌组织中的表达及其临床病理学意义.方法:用免疫组织化学法检测134例正常前列腺、良性前列腺增生和前列腺腺癌石蜡包埋组织中Cox-2、P504s、CK34βE12和P63的表达.结果:正常前列腺组织或良性前列腺增生组织未见或偶见P504s弱表达,但CK34βE12和P63均表达良好;前列腺腺癌组织中P504s表达良好,但CK34βE12和P63均表达消失,P504s表达阳性率为91.07%;与正常前列腺组和良性前列腺增生组相比.前列腺癌组的P504s阳性表达率存在显著性差异(p=0.001).COX-2在正常的前列腺组织几乎不表达,而良性前列腺增生组织及前列腺腺癌组织均可见阳性表达,阳性率分别为4.76%和80.36%;COX-2阳性表达率在正常前列腺组或良性前列腺增生组和前列腺腺癌组间有显著性差异(p=0.0027).COX-2与P504s表达存在相关性(r=0.377,P=0.039);COX-2的表达与年龄、临床分期、分化程度、有无远处转移等临床病理特征间无明显相关关系.结论:联合P504s、P63、CK34βE12和COX-2免疫组化检测可提高前列腺腺癌病理诊断的准确率.     

AnnexinⅠ蛋白在人前列腺癌中的表达及临床意义

目的：探讨AnnexinⅠ蛋白在前列腺癌组织中的表达及其与前列腺癌发生、发展、转移及预后的关系。方法：回顾性分析110例前列腺癌及40例前列腺增生组织中AnnexinⅠ蛋白的表达与前列腺癌Gleason分级、年龄、临床分期、转移及预后的相关性。结果：前列腺癌患者的AnnexinⅠ表达水平显著地低于良性前列腺增生症患者（P〈0．05）;AnnexinⅠ在低分化癌中表达较高,与高、中分化癌相比有显著性差异（P〈0．05）;而高、中分化癌之间AnnexinⅠ表达均较低,两者之间无显著性差异（P〉0．05）。前列腺癌AnnexinⅠ蛋白表达与年龄无关,而与临床分期、淋巴结转移及预后有关（P〈0．05）。结论：AnnexinⅠ蛋白表达下调与前列腺癌发生发展和预后密切相关,可作为反映前列腺癌生物学行为和判断预后的生物标记物.     

促红细胞生成素和受体在前列腺癌组织中共同过表达的研究

目的:探讨促红细胞生成素(EPO)和受体(EPOR)在前列腺癌(PCa)组织中的表达,并进一步阐述EPO和EPOR在前列腺癌发生发展中所起的作用。方法:应用免疫组化SP法检测30例前列腺癌根治术组织标本中癌与增生(BPH)组织的EPO和EPOR表达及30例正常前列腺组织(NP)中的EPO和EPOR表达。前列腺癌分级采用Gleason评分。半定量EPO和EPOR评分分析免疫组化结果。同时根据细胞染色强度区分为过表达和正常表达。统计学分析采用配对样本比较Wilcoxon的秩和检验及线形回归分析。结果:大部分前列腺癌均可见EPO和EPOR同时过表达,但是前列腺增生组织只有EPO过表达;正常前列腺组织没有EPO和EPOR过表达。前列腺癌和良性前列腺增生的EPO免疫组化评分中位数为2.38和0.93(P<0.01);前列腺癌和良性前列腺增生的EPOR免疫组化评分中位数为2.50和0.68(P<0.01)。前列腺增生和前列腺癌的EPO和EPOR表达密切相关,但是前列腺癌的Gleason评分和EPO以及EPOR评分没有相关性(P值均>0.05)。结论:EPO和EPOR同时过表达促进前列腺癌发生发展,但是相对于EPO的过表达,EPOR过表达是前列腺癌发生更为重要的早期事件;前列腺癌组织中EPO和EPOR表达差异,提示除了缺氧外,可能还有其它机制参与EPOR的过表达。     

CyclinD1、CDK4、P16和结核菌L型感染在前列腺癌中的表达及临床意义

目的探讨CyclinD1、CDK4和P16在前列腺癌中的表达以及结核菌L型感染率及临床意义。方法应用免疫组化和抗酸染色等方法检测了65例前列腺癌（carcinoma of prostate,PCa）和30例良性前列腺增生（benignprostatic hyperplasia,BPH）中的CyclinD1、CDK4和P16的表达,以及结核菌L型的检出率。并对前列腺肿瘤主要临床资料和病理分级参数进行比较,用χ^2检验进行统计学处理。结果 CyclinD1、CDK4阳性表达前列腺癌明显高于前列腺增生（P〈0.01）;并与前列腺癌的临床分期、病理分级及淋巴结转移差异有统计学意义（P〈0.01-0.05）呈正相关。P16阳性表达前列腺增生明显高于前列腺癌（P〈0.01）;与前列腺癌的临床分期、病理分级及淋巴结转移差异有统计学意义（P〈0.01-0.05）呈负正相关。结核菌L型检出率前列腺癌明显高于前列腺增生;与前列腺癌的临床分期、病理分级及淋巴结转移差异有统计学意义（P〈0.05）。结论 CyclinD1、CDK4和P16在前列腺肿瘤中不同程度异常表达以及结核菌L型检出率与肿瘤的临床分期、病理分级和转移相关,因此研究CyclinD1、CDK4和P16的阳性表达和结核菌L型感染与前列腺癌发生发展中可能有协同作用,具有重要的临床应用价值。     

VEGF、KDR和结核菌L型感染在前列腺癌中的表达及临床意义

目的 探讨血管内皮生长因子(VEGF)及其受体VEGFR-2(KDR)和结核菌L型感染在前列腺肿瘤中的表达及临床相关性研究.方法 应用免疫组化、原位杂交和抗酸染色等方法检测了65例前列腺癌(carcinoma of prostate,PCa)和30例良性前列腺增生(benign prostatic hyperplasia,BPH)中的VEGF、KDR蛋白及mRNA的表达,以及结核菌L型的检出率.并对前列腺肿瘤主要临床资料和病理分级参数进行比较,用χ2检验进行统计学处理.结果 VEGF、KDR蛋白及mRNA阳性表达和结核菌L型检出率前列腺癌明显高于前列腺增生(P<0.001～0.05).VEGF、KDR蛋白及mRNA阳性表达以及结核菌L型检出阳性率与前列腺癌的临床分期、病理分级差异有显著性(P<0.01～0.05).结论 VEGF及KDR蛋白及mRNA在前列腺肿瘤中有不同程度的异常表达,可能与结核菌L型感染有协同致瘤作用.提示2种基因均可作为判断前列腺癌生物学行为及患者预后参考指标.结核菌L型感染可能与前列腺癌的发生发展可能有一定关系,因此研究结核菌L型感染与前列腺癌的关系,具有重要的临床应用价值.     

Cox-2、P504s、CK34βE12和P63在前列腺腺癌中的表达及其临床意义

目的：研究Cox-2、P504s、CK34βE12和P63在前列腺腺癌组织中的表达及其临床病理学意义。方法：用免疫组织化学法检测134例正常前列腺、良性前列腺增生和前列腺腺癌石蜡包埋组织中Cox-2、P504s、CK34βE12和P63的表达。结果：正常前列腺组织或良性前列腺增生组织未见或偶见P504s弱表达,但CK34βE12和P63均表达良好;前列腺腺癌组织中P504s表达良好,但CK34βE12和P63均表达消失,P504s表达阳性率为91．07％;与正常前列腺组和良性前列腺增生组相比,前列腺癌组的P504s阳性表达率存在显著性差异（p=0．001）。COX-2在正常的前列腺组织几乎不表达,而良性前列腺增生组织及前列腺腺癌组织均可见阳性表达,阳性率分别为4．76％和80．36％;COX．2阳性表达率在正常前列腺组或良性前列腺增生组和前列腺腺癌组间有显著性差异（p=0．0027）。COX-2与P504s表达存在相关性（r=0．377,P=0．039）;COX-2的表达与年龄、临床分期、分化程度、有无远处转移等临床病理特征间无明显相关关系。结论：联合P504s、P63、CK3413E12和COX-2免疫组化检测可提高前列腺腺癌病理诊断的准确率。     

Frequent 14-3-3 sigma promoter methylation in benign and malignant prostate lesions

14-3-3Sigma is a putative tumor suppressor gene involved in cell cycle regulation and apoptosis following DNA damage. 14-3-3Sigma loss of expression has been reported is several human cancers, including prostate adenocarcinoma and precursor lesions, and promoter hypermethylation has been proposed as the mechanism underlying gene silencing. Here, we investigate the frequency and extent of 14-3-3sigma promoter methylation in benign and cancerous prostate tissues. We examined tumor tissue from 121 patients with prostate carcinoma (PCa), 39 paired high-grade prostatic intraepithelial neoplasias (HGPIN), 29 patients with benign prostate hyperplasia (BPH), as well as four prostate cancer cell lines using quantitative methylation-specific PCR (QMSP). The percentage of methylated alleles (PMA) was calculated and correlated with clinical and pathological parameters. RT-PCR was performed in the cell lines to assess 14-3-3sigma mRNA expression. PCa, HGPIN, BPH, and cancer cell lines showed ubiquitous 14-3-3sigma promoter methylation. However, the PMA of HGPIN was significantly lower than that of PCa or BPH (P < 0.0001), while PCa and BPH did not significantly differ. The PMA did not correlate with any clinicopathological parameter. All prostate cancer cell lines expressed 14-3-3sigmamRNA. 14-3-3Sigma promoter methylation is a frequent event in prostate tissues and cancer cell lines. Furthermore, there is a progressive accumulation of neoplastic cells with 14-3-3sigma methylated alleles from HGPIN to PCa, suggesting a role for this epigenetic event in prostate carcinogenesis. However, other mechanisms besides promoter methylation might be required for effective 14-3-3sigma downregulation.     

Nuclear Ep-ICD Expression Is a Predictor of Poor Prognosis in “Low Risk” Prostate Adenocarcinomas

IntroductionMolecular markers for predicting prostate cancer (PCa) that would have poor prognosis are urgently needed for a more personalized treatment for patients. Regulated intramembrane proteolysis of Epithelial cell adhesion molecule results in shedding of the extracellular domain (EpEx) and release of its intracellular domain (Ep-ICD) which triggers oncogenic signaling and might correlate to tumor aggressiveness. This study aimed to explore the potential of Ep-ICD and EpEx to identify PCa that have poor prognosis.MethodsImmunohistochemical analysis of Ep-ICD and EpEx was carried out in normal prostate tissues (n = 100), benign prostate hyperplasia (BPH, n = 83), and prostate cancer (n = 249) using domain specific antibodies. The expression of Ep-ICD and EpEx was correlated with clinico- pathological parameters and disease free survival (DFS).ResultsReduced expression of nuclear Ep-ICD and membrane EpEx was observed in PCa in comparison with BPH and normal prostate tissues (p = 0.006, p < 0.001 respectively). For patients who had PCa with Gleason Score less than 7, preserved nuclear Ep-ICD emerged as the most significant marker in multivariate analysis for prolonged DFS, where these patients did not have recurrence during follow up of up to 12 years (p = 0.001).ConclusionReduced expression of nuclear Ep-ICD was associated with shorter disease free survival in patients with a Gleason Score less than 7 and may be useful in identifying patients likely to have aggressive tumors with poor prognosis. Furthermore, nuclear Ep-ICD can differentiate between normal and prostate cancer tissues for ambiguous cases.     

Proteomic analysis of formalin-fixed prostate cancer tissue

Proteomic analysis of formalin-fixed paraffin-embedded (FFPE) tissue would enable retrospective biomarker investigations of this vast archive of pathologically characterized clinical samples that exist worldwide. These FFPE tissues are, however, refractory to proteomic investigations utilizing many state of the art methodologies largely due to the high level of covalently cross-linked proteins arising from formalin fixation. A novel tissue microdissection technique has been developed and combined with a method to extract soluble peptides directly from FFPE tissue for mass spectral analysis of prostate cancer (PCa) and benign prostate hyperplasia (BPH). Hundreds of proteins from PCa and BPH tissue were identified, including several known PCa markers such as prostate-specific antigen, prostatic acid phosphatase, and macrophage inhibitory cytokine-1. Quantitative proteomic profiling utilizing stable isotope labeling confirmed similar expression levels of prostate-specific antigen and prostatic acid phosphatase in BPH and PCa cells, whereas the expression of macrophage inhibitory cytokine-1 was found to be greater in PCa as compared with BPH cells.     

Combined hypermethylation of APC and GSTP1 as a molecular marker for prostate cancer: quantitative pyrosequencing analysis

A total of 149 human prostate tissues obtained from our institute were assessed: 52 specimens of benign prostate hyperplasia (BPH) and 97 specimens of prostate cancer (PCa). The methylation status of the genes of Adenomatous polyposis coli (APC) and glutathione-S-transferase-P1 (GSTP1) was analyzed by quantitative pyrosequencing. A methylation score (M score) was calculated to capture the combined methylation level of both genes. The methylation level of each single gene and that of both genes combined was significantly higher in PCa specimens than in BPH (each p < 0.001). The value of APC methylation, GSTP1 methylation, and M score for predicting PCa was measured by the area under the receiver operating characteristic (ROC) curve and reached 0.954, 0.942, and 0.983, respectively. The sensitivity and specificity of the M score in discriminating between PCa and BPH reached 92.8% and 100.0%, respectively. The M score was positively associated with the serum prostate-specific antigen (PSA) level (p trend < 0.001). Our study demonstrates that the quantitative measurement of two methylation markers might drastically improve the ability to discriminate PCa from BPH.     

前列腺PI-RADS V2.1评分联合血清PSA相关指标对灰区前列腺癌的诊断价值研究

摘要 目的：探讨前列腺影像报告和数据系统第2.1版（PI-RADS V2.1）评分联合血清前列腺特异抗原（PSA）相关指标对灰区前列腺癌的诊断价值。方法：回顾性分析2016年1月至2019年12月的187例经病理证实且PSA为灰区（4-10 ng/mL）的前列腺癌或前列腺增生患者资料。根据病理结果分为前列腺癌（PCa）组与前列腺增生组（BPH）组。由两名经验丰富的MRI诊断医师通过盲法对所有患者MRI图像进行PI-RADS V2.1评分,统计并计算血清PSA相关指标：总前列腺特异抗原（t-PSA）、游离前列腺特异抗原（f-PSA）、游离前列腺特异抗原与总前列腺特异抗原比值（f-PSA/t-PSA）、前列腺特异抗原密度（PSAD）。采用t检验比较各项指标在两组间的差异性,并使用受试者工作曲线（ROC）分析各项指标对灰区前列腺癌的诊断效能。结果：PI-RADS V2.1评分与PSAD在PCa与BPH组之间的差异具有统计学意义（P＜0.05）,而t-PSA、f-PSA、f-PSA/t-PSA在PCa与BPH组之间的差异均无统计学意义（P＞0.05）。根据ROC曲线分析,PI-RADS V2.1评分、PSAD、PI-RADS V2.1评分联合PSAD诊断灰区前列腺癌的曲线下面积（AUC）分别为0.814、0.671及0.838,且PI-RADS V2.1评分联合PSAD的AUC显著高于单独应用PI-RADS V2.1评分（Z=1.989,P＜0.05）与PSAD（Z=3.174,P＜0.05）。结论：PI-RADS V2.1评分与PSAD对诊断灰区前列腺癌具有较高诊断效能,且联合PI-RADS V2.1评分与PSAD能进一步提高诊断效能。     

Up‐regulation of LIMK1 expression in prostate cancer is correlated with poor pathological features,lymph node metastases and biochemical recurrence

This study aimed to explore the association between LIM domain kinase 1 (LIMK1) expression in prostate cancer (PCa) tissues with advanced pathological features, lymph node metastases and biochemical recurrence. A total of 279 PCa specimens from patients who underwent radical prostatectomy and 50 benign prostatic hyperplasia (BPH) specimens were collected to construct tissue microarray, which were subjected to immunohistochemical staining for LIMK1 expression subsequently. Logistic and Cox regression analysis were used to evaluate the relationship between LIMK1 expression and clinicopathological features of patients with PCa. Immunohistochemical staining assay demonstrated that LIMK1 expression was significantly higher in PCa than BPH specimens (77.1% vs 26.0%; P < .001). LIMK1 expression was significantly higher in positive lymph node specimens than corresponding PCa specimens (P = .002; P < .001). Up‐regulation of LIMK1 was associated with prostate volume, prostate‐specific antigen, prostate‐specific antigen density, Gleason score, T stage, lymph node metastases, extracapsular extension and seminal vesicle invasion, and positive surgical margin. Multivariate logistic regression analysis demonstrated that LIMK1 was an independent risk factor for PCa lymph node metastasis (P < .05). Multivariate Cox regression analysis revealed that the up‐regulation of LIMK1 was an independent risk factor for biochemical recurrence. Kaplan‐Meier analysis indicated that up‐regulation LIMK1 was associated with shortened biochemical‐free survival (BFS) after radical prostatectomy (P < .001). In conclusion, LIMK1 was significantly up‐regulated in PCa and positive lymph node specimens and correlated with lymph node metastasis and shortened BFS of PCa. The underlying molecular mechanism of LIMK1 in PCa should be further evaluated.     

COX-2、Ki-67和结核菌L型感染在前列腺癌中的表达

目的探讨环氧合酶-2（COX-2）和Ki-67在前列腺癌中的表达以及结核菌L型感染率及临床意义。方法应用免疫组化、原位杂交和抗酸染色等方法检测了65例前列腺癌（carcinoma of prostate,PCa）和30例良性前列腺增生（benign prostatic hyperplasia,BPH）中的COX-2、Ki-67蛋白及mRNA的表达,以及结核菌L型的检出率;并对前列腺肿瘤主要临床资料和病理分级参数进行比较,用χ^2检验进行统计学处理。结果COX-2、Ki-67蛋白及mRNA阳性表达和结核菌L型检出率,前列腺癌明显高于前列腺增生（P〈0.001～0.05）。COX-2、Ki-67蛋白及mRNA阳性表达和结核菌L型检出率与前列腺癌的临床分期、病理分级有明显差异（P〈0.01～0.05）。淋巴结转移组中COX-2、Ki-67蛋白及mRNA的阳性表达率明显高于非转移组（P〈0.01）。结核菌L型检出率淋巴结转移组明显高于非转移组（P〈0.05）。结论COX-2、Ki-67蛋白及mRNA在前列腺肿瘤中不同程度异常表达以及结核菌L型检出率与肿瘤的临床分期、病理分级和转移呈正相关,提示2种基因均可作为判断前列腺癌生物学行为及患者预后参考指标。结核菌L型感染极有可能导致基因的变异或过表达,成为诱发肿瘤因素之一,它们可能有协同致瘤作用。