前列腺干细胞抗原在人前列腺癌组织中的表达及意义

目的　探讨前列腺干细胞抗原 (PSCA)在国人前列腺癌 (PCa)组织中表达的临床意义。　方法　采用免疫组织化学 (IHC)和核酸原位杂交 (ISH)方法检测 4 0例PCa、2 0例良性前列腺增生(BPH)和 2 0例前列腺上皮内瘤 (PIN)组织标本PSCA蛋白和mRNA表达 ,半定量法计算PSCA阳性表达细胞百分数和阳性表达强度 ,比较各组织间表达水平的差异及其与PCa分级、临床分期之间的关系。　结果　PCa、BPH、PIN组织PSCA中度阳性到强阳性表达分别为 85 % (34/ 4 0 )、2 0 % (4/ 2 0 )和35 % (7/ 2 0 ) ;PCa组织PSCA表达水平与BPH和PIN比较差异有统计学意义 (P <0 .0 5 ) ,BPH与PIN比较差异无统计学意义 (P >0 .0 5 ) ;PCa组织PSCA表达水平随Gleason评分及临床分期增加而升高。　结论　人PCa组织有PSCA蛋白质和mRNA的过表达 ,且与PCa病理分级、临床分期呈正相关 ,可能对PCa的诊断及判断预后有潜在价值。     

全雄激素阻断治疗抑制人前列腺癌前列腺干细胞抗原mRNA的表达

目的观察全雄激素阻断（CAA）治疗前后前列腺干细胞抗原（PSCA）mRNA 表达水平的变化,并进一步评估 PSCA 在人前列腺癌的临床预后价值。方法对42例男性患者的前列腺活检组织或经尿道前列腺切除组织（包括去势前局限性前列腺癌组织和前列腺癌根治术前接受比卡鲁胺和醋酸戈舍瑞林去势治疗3个月后的癌组织）进行原位杂交。PSCA mRNA 的肿瘤细胞质染色结果由两位病理学专家独立评估,t 检验分析 CAA 前后 PSCA mRNA 表达水平的差异。前列腺癌根治术后进行36~40个月的随访,旨在评估 PSCA mRNA 表达水平与癌症局部复发或转移的相关性。结果原位杂交标记 PSCA mRNA 阳性的细胞由 CAA 前的67.3%（0~89%）±9.4%下降到 CAA 后33.8%（0~92%）±7.7%（P 〈0.001）。CAA 前95.2%（40/42）的患者 PSCA mRNA 表达阳性,而去势后阳性率降到67.5%（27/40）,且随访未发现有局部复发或远处转移。PSCA mRNA 阳性表达的减少取决于原始肿瘤的 Gleason 评分,Gleason≤6：19.3%±4.7%;Gleason=7：38.8%±7.2%;Gleason≥8：73.4%±13.8%（P 〈0.05）。其余13例,CAA 后 PSCA mRNA 阳性表达水平增加,且随访发现3例有局限复发,4例有远处转移。结论前列腺癌 CAA 可抑制 PSCA mRNA 的表达;去势治疗后 PSCA mRNA 表达的增加可成为肿瘤复发或远处转移的一个不利预测指标。     

位于8q24的NOV和WISP-1基因在前列腺癌的表达

目的 探讨定位于8q24的CCN家族成员NOV基因和WISP-1基因在前列腺癌的表达.方法 采用半定量的RT-PCR方法和免疫组化法分析37例前列腺癌组织和10例正常前列腺组织中NOV和WISP-1的mRNA和蛋白的表达.结果 37例前列腺癌组织和10例正常前列腺组织中均检测到NOV mRNA表达,前列腺癌的表达水平显著高于正常前列腺组织(P<0.05),而且T3,T4期前列腺癌的表达水平显著高于T1,T2期前列腺癌(P<0.05).在37例前列腺癌中有24例(64.7%)检测到WISP-1的mRNA表达,而正常前列腺组织中均为阴性,差异具统计学意义(P<0.05).免疫组化研究显示前列腺癌组织的NOV蛋白染色强度明显高于正常前列腺组织(P<0.05).正常前列腺组织和前列腺癌组织均未检测到WISP-1蛋白.结论 NOV基因在前列腺癌的发生发展过程中起着重要作用.     

EZH2在前列腺癌中的表达及其与临床病理的关系

目的:探讨EZH2蛋白及其mRNA在前列腺癌中的表达以及两者与临床病理参数间的关系。方法:通过组织芯片技术,运用免疫组化(EnVision法)和原位杂交方法分别检测48例前列腺癌中EZH2蛋白及其mRNA的表达,同时检测常规石蜡组织中15例良性前列腺增生组织和12例高级别上皮内瘤变组织中的EZH2蛋白及其mRNA的表达作为对照。结果:EZH2蛋白和mRNA在前列腺癌中的阳性率(87.5%、81.25%)明显高于良性前列腺增生组织(13.33%、6.67%)和高级别上皮内瘤(16.67%、16.67%),差异有统计学意义(P<0.05)。免疫组化显示,EZH2蛋白在Gleason≥7分组阳性表达率(96.67%)明显高于Gleason≤6分组(72.22%),差异有统计学意义(P<0.05)。EZH2蛋白阳性表达率与TNM分期比较,T3～T4期(100%)明显高于T1～T2期(76.92%),亦有统计学意义(P<0.05),而EZH2蛋白表达与年龄和PSA无关(P>0.05)。原位杂交显示,EZH2mRNA的阳性表达率T3～T4期(100%)高于T1～T2期(85%),与TNM分期显著相关(P<0.05),而与年龄、PSA和Gleason分级无关(P>0.05)。分段评价预后估计较好组与预后估计较差组,两组之间EZH2蛋白及其mRNA表达阳性率均有显著性差异(P<0.05)。结论:EZH2蛋白及其mRNA在前列腺癌中高表达,提示其在前列腺癌的发生、发展过程中可能起重要作用,有可能成为判定前列腺癌恶性程度进程和预后的参考指标。     

前列腺癌组织中前列腺干细胞抗原的表达及其意义

目的 :探讨前列腺癌 (PCa)组织中前列腺干细胞抗原 (prostatestemcellantigen ,PSCA)的表达及其意义。方法 :应用核酸分子原位杂交 (ISH)技术 ,对 2 6例PCa和 9例正常前列腺 (NP)组织中PSCAmRNA进行检测和定位。结果 :PSCAmRNA在PCa组织表达阳性率为 84 .6 % ,其中强阳性率为 5 7.7% ;NP组织阳性率为6 6 .7% (均为弱阳性 )。PCa与NP组织表达水平差异有极显著性意义 (P <0 .0 1)。PSCAmRNA在PCa组织主要表达于癌细胞 ,细胞间质和肌肉组织均无表达 ;NP组织表达则定位于前列腺上皮的基底细胞层。PSCAmR NA表达水平与PCa临床分期、病理分级均无相关性 (P >0 .0 5 )。结论 :PSCA在探索PCa起源、PCa免疫靶向治疗方面有重要意义     

前列腺干细胞抗原在前列腺癌中的表达及其与雄激素受体、雌激素受体联合检测的意义

目的探讨前列腺干细胞抗原(PSCA)在前列腺癌(PCa)和良性前列腺增生(BPH)中的表达,及其与雄激素受体(AR)、雌激素受体(ER)联合检测的临床意义。方法应用免疫组化方法检测PSCA、AR和ER在50例PCa和30例BPH标本中的表达。结果 PSCA在PCa中高表达,在BPH中少量表达或不表达,PSCA表达的变化与PCa的Gleason评分具有明显相关性。AR在PCa中的表达与其分化程度无明显相关性,与PSCA无明显相关性。ER在BPH中表达阳性率为100%,且普遍强阳性,在PCa中表达的阳性率为12%,均与PSCA的表达呈负相关。结论 PSCA在前列腺细胞增殖、肿瘤形成的演进过程中发挥重要作用,联合检测PSCA和ER有助于PCa和BPH的诊断和治疗。     

JKTBP在前列腺癌细胞系和组织中的表达差异及其意义

目的 研究在雄激素依赖性及雄激素非依赖性前列腺癌细胞系、组织和前列腺增生(BPH)组织中JKTBP的表达差异.方法 应用RT-PCR和Western blot比较雄激素依赖性前列腺癌(AD-PCa)细胞系LNCaP及雄激素非依赖性前列腺癌(AI-PCa)细胞系DU145 JKTBP mRNA和蛋白的表达差异;应用免疫组化方法比较BPH、AD-PCa和AI-PCa组织中JKTBP的表达差异.结果 在LNCaP细胞系中JKTBP mRNA和蛋白的表达水平均较低,相反,在DU145细胞系中两者均呈高表达,两细胞系间mRNA和蛋白的表达差异具有统计学意义(P<0.05).JKTBP在20例BPH组织中均表达阴性;在20例AD-PCa组织中有4例弱阳性,2例阳性,14例阴性;而在6例AI-PCa组织中5例呈强阳性表达,1例弱阳性;三组之间表达差异具有统计学意义(P<0.05).结论 JKTBP在AD/AI-PCa细胞系、组织和BPH组织中的表达存在差异,其可能参与了前列腺癌的进展过程,是前列腺癌进展的一个指标.     

组织激肽释放酶基因7在前列腺癌组织中的表达

目的 探讨组织激肽释放酶基因7(KLK7)在不同前列腺组织中的表达情况.方法运用逆转录聚合酶链反应法检测正常前列腺(5例)、良性前列腺增生(BPH)及BPH细胞株(BPH1,13例)、前列腺癌及前列腺癌细胞株(8例)的上皮细胞中KLK7mRNA表达水平;蛋白质印迹法检测不同前列腺组织上皮细胞中KLK7蛋白表达水平;免疫组化分析正常前列腺(20例)、BPH(50例)、前列腺癌(103例)组织中KLK表达水平.根据染色强度分为4个等级(-,+,++,+++)进行半定量分析,染色强度++及+++者判定为阳性.结果 正常组、BPH组和前列腺癌组KLK7 mRNA表达相对值分别为0.59、0.52、0.02,组间比较差异有统计学意义(F=13.03,P＜0.01),前列腺癌上皮中KLK7 mRNA表达下调(P＜0.01),正常前列腺和BPH上皮中KLK7 mRNA表达差异无统计学意义(P＞0.05).KLK7蛋白在正常前列腺、增生前列腺、DU145、LNCaP、PC3、22RV1、BPH细胞株中表达水平相对值分别为0.22、0.40、0.01、0.05、0、0.03、0.14.免疫组化染色结果 显示正常前列腺组织、BPH组织、前列腺癌中KLK7蛋白表达阳性率分别为65.0%(13/20)、76.0%(38/50)、17.5%(18/103),前列腺癌组与前2组比较差异均有统计学意义(P＜0.01),前2组间比较差异无统计学意义(P＞0.05).结论 KLK7在前列腺癌组织中表达下调,提示KLK7在前列癌的发生和进展中可能起一定作用.     

人前列腺干细胞抗原在前列腺组织中的表达

目的：克隆人前列腺干细胞抗原(PSCA)基因，并利用半定量逆转录聚合酶链反应(RT—PCR)对其组织表达谱进行分析。方法：从人前列腺癌组织提取总RNA，利用RT—PCR技术扩增出人PSCA基因编码区序列，并通过半定量RT—PCR方法检测6例人新鲜正常前列腺组织、16例前列腺增生组织及11例前列腺肿瘤组织中PSCA基因表达水平。结果：序列测定表明，克隆获得的369bp片段与文献报道的人PSCA基因编码区cDNA序列一致，PSCA为前列腺组织特异表达，在前列腺癌组织中的表达明显高于前列腺增生及前列腺正常组织。结论：PSCA是一种新的前列腺肿瘤标记物。     

人晚期糖基化产物受体在前列腺癌和正常前列腺组织的表达差异

目的:研究人晚期糖基化产物受体(receptor for advanced glycation end product,RAGE)在前列腺癌和正常前列腺组织中的表达差异,为进一步研究RAGE在前列腺癌发病机制中的作用奠定基础。方法:以同一患者的前列腺癌组织和正常前列腺组织配对作比较,采用免疫组化染色法、免疫印迹法、实时荧光定量PCR等方法分别从组织水平、蛋白质水平、mRNA水平检测10例患者前列腺癌和正常前列腺组织中RAGE的表达。结果:免疫组化结果显示RAGE在前列腺癌组织中的表达水平明显高于正常前列腺组织,Western印迹检测发现前列腺癌组织RAGE的表达量是正常前列腺组织的2.13倍(Р<0.05),荧光定量PCR检测前列腺癌中RAGE的mRNA表达水平是正常前列腺组织的4.2倍(Р<0.05)。结论:RAGE在前列腺癌的发生和发展过程中可能起重要作用。     

Complete androgen ablation suppresses prostate stem cell antigen (PSCA) mRNA expression in human prostate carcinoma

BACKGROUND: Prostate stem cell antigen (PSCA) is a recently identified glycosylphosphatidylinositol (GPI)-anchored cell surface protein belonging to the Thy-1/Ly-6 family of cell surface antigens. Prior data in prostate cancers indicated that PSCA is directly regulated by androgens and PSCA expression increases with high-tumor grade, advanced stage, extracapsular invasion, and androgen-independent progression. The effect of complete androgen ablation (CAA) on tumor PSCA mRNA expression has not been elucidated. The purpose of the present study was to investigate the variations in the expression levels of PSCA mRNA before and after CAA, and further evaluate the clinically prognostic value of PSCA in human prostate carcinoma. MATERIALS AND METHODS: PSCA in situ hybridization (ISH) was performed on the cancerous pretreatment biopsy or transurethral resection of prostate (TURP) tissue of 42 men with primarily organ-confined prostate cancer before CAA, and on their tumor tissue from radical retropubic prostatectomy after CAA with bicalutamide and goserelin acetate for 3 months prior to undergoing radical prostatectomy. Tumor cytoplasmic staining of PSCA mRNA was evaluated by two independent pathologists and the differences of PSCA mRNA expression levels between the samples before and after CAA were analyzed using the Student's t-test. Thirty-six to forty months follow-up studies after radical retropubic prostatectomy were performed and aimed at assessing the correlation of PSCA mRNA expression level with local recurrences or metastases from the cancer. RESULTS: The percent of cells positive for PSCA mRNA by ISH labeling declined from 67.3% (0-89%)+/-9.4% before CAA to 33.8% (0-92%)+/-7.7% after CAA (P<0.001). Before CAA, 40 of 42 cases (95.2%) were positive for PSCA mRNA labeling, however, after CAA the percentage of positive reactivity of PSCA mRNA was decreased to 27 of 40 cases (67.5%), in which none was found with local recurrences or distant metastases after radical prostatectomy on follow-up. This decline in PSCA mRNA labeling was dependent on the original tumor grade with Gleason score of or=8: 73.4%+/-13.8% (P<0.05, respectively). The rest 13 cases had the increased percentage of cells positive for PSCA mRNA after CAA, in which 3 cases were found with local recurrences and 4 cases with distant metastases from tumor on follow-up. CONCLUSIONS: Our data demonstrate that CAA for prostate cancer can suppress PSCA mRNA expression with a tumor grade dependence and the increased expression of PSCA mRNA after CAA may be a clinically adverse predictor for tumor recurrences or distant metastases.     

Prostate stem cell antigen (PSCA) mRNA expression in prostatic intraepithelial neoplasia: implications for the development of prostate cancer

BACKGROUND: Prior data clearly demonstrated the expression of prostate stem cell antigen (PSCA) mRNA in prostatic intraepithelial neoplasia (PIN) tissues. The purpose of the present investigation was to determine whether PSCA mRNA expression was associated with the presence of cancer in this disease. METHODS: One hundred seventeen men were diagnosed with isolated PIN on initial prostate biopsy, 51 with low-grade form (LGPIN), and 66 with high-grade form (HGPIN). PSCA mRNA expression in initial PIN and subsequent cancer was examined by in situ hybridization (ISH). The differences of the PSCA mRNA expression level between the groups were analyzed by the Chi-square and Student's t-test. Univariate and multivariate logistic regression analyses were performed to evaluate the predictive performance of PSCA mRNA. RESULTS: PSCA mRNA expression level in 34 subsequent cancers was statistically increased compared with their paired PIN (P < 0.001), with a Gleason's dependence. HGPIN showed statistically high PSCA mRNA expression compared with LGPIN (P < 0.01). PSCA mRNA expression levels were significantly stronger in the initial isolated LGPIN and isolated HGPIN with subsequent cancer than those without (P < 0.001 and P < 0.001, respectively). Multivariate logistic regression analysis demonstrated that only PSCA mRNA was predictive of the onset of subsequent cancer in patients with isolated LGPIN and in those with isolated HGPIN, respectively. CONCLUSIONS: Our data identify PSCA mRNA in initial PIN as a significant predictor of subsequent cancer, suggesting that PSCA implies in prostatic tumorigenesis and may be used to identify the patients with isolated PIN who are at high risk for cancer onset in the disease process.     

External beam radiotherapy (EBRT) suppressed prostate stem cell antigen (PSCA) mRNA expression in clinically localized prostate cancer

BACKGROUND: Prostate stem cell antigen (PSCA), a recently identified glycosylphosphatidylinositol (GPI)-anchored cell surface protein belonging to the Thy-1/Ly-6 family of cell surface antigens, is overexpressed in human prostate cancer (PCa). Our recent data indicated that complete androgen ablation could significantly suppress PSCA mRNA expression in primarily organ-confined PCa. The effect of external beam radiotherapy (EBRT), one of the curative treatment options for localized PCa, on tumor PSCA mRNA expression has not been elucidated. The purpose of the present study was to investigate the variations in the expression levels of PSCA mRNA before and after EBRT, and further evaluate the prognostic value of PSCA in this disease. MATERIALS AND METHODS: Between January 1999 and June 2005, 87 men with clinically localized adenocarcinoma of the prostate received only EBRT with a total dose of 65-70 Gy for 6.5-7 weeks. PSCA in situ hybridization (ISH) was performed on the cancerous pretreatment biopsy or transurethral resection of prostate (TURP) tissue and post-treatment biopsy tissue of all 87 men, respectively. Tumor cytoplasmic staining of PSCA mRNA was evaluated by two independent pathologists and the differences of PSCA mRNA expression levels between the samples before and after EBRT were analyzed using the Student's t-test. Twenty-four to seventy months continuous follow-up studies after treatment were performed and aimed at assessing the correlation of PSCA mRNA expression level with biochemical relapse and/or distant metastases from the cancer. RESULTS: The percent of cells positive for PSCA mRNA by ISH labeling declined from 71.2% (0-93%) +/- 9.7% before EBRT to 30.7% (0-90%) +/- 5.3% after EBRT (P<0.001). Before EBRT, 81 of 87 cases (93.1%) were positive for PSCA mRNA labeling, however, after EBRT the percentage of positive reactivity of PSCA mRNA was decreased to 62 of 81 cases (76.5%), in which 59 men (95.2%) were found without biochemical relapse or distant metastases on follow-up. This decline in PSCA mRNA labeling was directly proportional to higher pretreatment serum PSA level, higher tumor grade (Gleason score), and higher clinical T stage. The rest 19 cases had the increased percentage of cells positive for PSCA mRNA after EBRT, in which 15 cases developed biochemical relapse and/or distant metastases from tumor on follow-up. CONCLUSIONS: We found that EBRT for PCa can significantly suppress PSCA mRNA expression and the elevated PSCA mRNA level after EBRT may be a clinically adverse predictor for tumor progression.     

The association of prostate stem cell antigen (PSCA) mRNA expression and subsequent prostate cancer risk in men with benign prostatic hyperplasia following transurethral resection of the prostate

BACKGROUND: Prior data showed prostate stem cell antigen (PSCA) mRNA expression in benign prostatic hyperplasia (BPH) tissues. The purpose of the present investigation was to determine whether PSCA mRNA expression in resected BPH samples was associated with the subsequent presence of cancer following transurethral resection of the prostate (TURP). METHODS: PSCA in situ hybridization was performed on the TURP-resected tissues from 288 patients, who were histopathologically confirmed BPH without cancer. All these patients were continuously followed for 9-70 months postoperatively. Univariate and multivariate cox regression analyses were used to evaluate the predictive performance of PSCA mRNA for subsequent cancer onset following TURP. RESULTS: PSCA mRNA was detected in 93/288 (32.3%) of the resected BPH specimens, with a mean positive-labeling cells of 23.8%, in which 22 patients (23.7%) were identified as having PCa on follow-up. Of 195 patients with negative expression for PSCA mRNA 2 (1.0%) were subsequently found with PCa. PSCA mRNA expression levels were directly proportional to higher Gleason score and clinical T stage. Univariate and multivariate cox regression analyses demonstrated that only PSCA mRNA expression was predictive of the subsequent cancer development after TURP, however, PSA velocity was an univariately significant but not multivariately significant predictor. CONCLUSIONS: This prospective study identifies PSCA mRNA in BPH as a significant predictor of cancer development after TURP, suggesting that PSCA may be used to identify patients who are at high risk for subsequent cancer onset following TURP for BPH and the PSCA test may be useful when applied for repeat biopsies.     

Human epidermal growth factor receptor type 2 protein expression in Chinese metastatic prostate cancer patients correlates with cancer specific survival and increases after exposure to hormonal therapy

Aim： To investigate human epidermal growth factor receptor type 2 （HER2） protein expression and gene amplification in Chinese metastatic prostate cancer patients and their potential value as prognostic factors. Methods： Immunohistochemistry （IHC） was performed to investigate HER2 protein expression in prostate biopsy specimens from 104 Chinese metastatic prostate cancer patients. After 3-11 months of hormonal therapy, 12 patients underwent transurethral resection of the prostate （TURP）. HER2 protein expression of TURP specimens was compared with that of the original biopsy specimens. Of these, 10 biopsy and 4 TURP specimens with HER2 IHC staining scores ≥ 2＋ were investigated for HER2 gene amplification status by fluorescent in situ hybridization （FISH）. Results： Of the 104 prostate biopsy specimens, HER2 protein expression was 0, 1＋, 2＋ and 3＋ in 49 （47.1%）, 45 （43.3%）, 8 （7.7%） and 2 （1.9%） cases, respectively. There was a significant association between HER2 expression and Gleason score （P = 0.026）. HER2 protein expression of prostate cancer tissues increased in 33.3% of patients after hormonal therapy. None of the 14 specimens with HER2 IHC scores 〉 2＋ showed HER2 gene amplification. Patients with HER2 scores 〉 2＋ had a significantly higher chance of dying from prostate cancer than those with HER2 scores of 0 （P = 0.004） and 1＋ （P = 0.034）. Multivariate Cox regression analysis showed that HER2 protein expression intensity was an independent predictor of cancer-related death （P = 0.039）. Conclusion： An HER2 IHC score 〉 2＋ should be defined as HER2 protein overexpression in prostate cancer. Overexpression of HER2 protein in cancer tissue might suggest an increased risk of dying from prostate cancer. HER2 protein expression increases in some individual patients after hormonal therapy.