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.     

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.     

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.     

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。     

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     

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.     

Clinical relevance of transurethral resection of the prostate in "asymptomatic" patients with an elevated prostate-specific antigen level

OBJECTIVES: To determine the clinical relevance of transurethral resection of the prostate (TURP) in patients with minor lower urinary tract symptoms (LUTS) but elevated prostate-specific antigen (PSA) levels. METHODS: We retrospectively included 82 patients, aged 50.2-78.2 yr, with minor LUTS, elevated PSA (> or =4 ng/ml), and no signs of prostate cancer (PCa) after (multiple) negative multisite biopsies who underwent TURP after they were diagnosed by urodynamics with bladder outlet obstruction (BOO). We evaluated the clinical benefit of TURP by assessing its effect on International Prostate Symptom Score (IPSS) and PSA and the diagnostic value of histologic examination of the resected tissue for the presence of PCa. RESULTS: After TURP, histologic analysis of the resected specimen revealed that eight patients (9.8%) had PCa; seven of these patients had a tumour that needed further treatment. The remaining 74 patients (90.2%) were diagnosed with BOO due to benign prostatic hyperplasia/benign prostatic enlargement (BPH/BPE). In this group, the mean PSA level decreased from 8.8 ng/ml before TURP to 1.1 ng/ml in the first year and 1.3 ng/ml in the second year after TURP; the mean IPSS decreased from 8.8 to 1.5 in the first year after TURP. CONCLUSIONS: The current data suggest that patients with minor LUTS and elevated PSA without evidence of PCa are very likely to have BOO due to BPH/BPE and may benefit from TURP if obstruction is proved. However, a prospective trial is warranted to assess the impact of these results on clinical practice.     

前列腺癌组织中前列腺癌抗原-1的表达及临床意义

目的:探讨PCa组织中前列腺癌抗原-1(PCA-1)的表达及其临床意义。方法:采用逆转录-聚合酶链反应(RT-PCR)技术,检测45例PCa组织、30例前列腺高分级上皮样内瘤样病变组织(HG-PIN)、43例BPH组织和39例其他肿瘤组织标本中PCA-1 mRNA的表达。免疫组织化学检测不同前列腺组织中PCA-1蛋白的表达。结果:PCa与HG-PIN组织标本中PCA-1 mRNA的阳性表达率分别为80.0%(36/45)和60.0%(18/30),BPH组织及其他肿瘤组织中均未见PCA-1 mRNA的表达。PCA-1 mRNA表达与PCa的临床病理参数之间无明显相关性,差异均无统计学意义(P>0.05)。PCa与HG-PIN组织标本中PCA-1蛋白的阳性表达率分别为75.6%(34/45)和50.0%(15/30),BPH组织及其他肿瘤组织中未见PCA-1蛋白阳性表达。结论:PCA-1仅在PCa组织中表达,且与PCa的临床病理参数无关,有可能作为特异性的肿瘤标志物对PCa进行早期诊断。     

DD3 mRNA在前列腺癌组织中定量表达分析

目的:探讨DD3基因在前列腺组织中表达的临床意义。方法:用荧光定量RT-PCR方法对21例前列腺癌(PCa)组织、27例非前列腺部位的肿瘤组织、39例良性前列腺增生(BPH)组织和15例正常前列腺组织中的DD3的表达进行了定量分析,用ROC曲线对DD3 mRNA诊断PCa的性能进行了分析。结果:27例非前列腺组织中均未检测到DD3基因的表达。DD3在PCa组、BPH组和正常前列腺组表达量的中位数分别为7.2×106、2.5×104、1.5×104拷贝/mg组织。PCa组较BPH组和正常前列腺组DD3的表达量显著增高(P<0.01),而BPH组和正常前列腺组间则差异无显著性(P>0.05)。DD3表达量与临床分期和分化程度之间均无明显相关性。DD3 mRNA曲线下面积(AUC-ROC)为0.937(95%CI:0.879～0.995)。当临界值为1.4×105拷贝/mg组织时,灵敏度、特异度、准确度、阳性预测值(PPV)、阴性预测值(NPV)、阳性拟然比(+LR)、阴性拟然比(-LR)分别为90.5%、85.0%、86.7%、76.0%、94.3%、6.03和0.11。结论:DD3 mRNA的表达仅限于前列腺组织,具有良好的组织特异性。DD3 mRNA表达在PCa组织中显著升高,在正常前列腺和BPH组织中差异无显著性。DD3 mRNA可作为PCa诊断的良好标志物,在PCa早期诊断、微转移诊断、预后判断、指导治疗等方面也具有潜在的应用价值。     

诊断性前列腺电切术对血清PSA异常患者的应用研究

目的:探讨诊断性前列腺电切(TURP)在前列腺增生合并血清PSA异常患者中的应用价值及意义,为临床处理前列腺增生合并血清PSA异常的患者提供一种新的手段。方法:收集符合入组标准的患者71例,总结病理为前列腺癌患者的Gleason评分及预后。对所有患者进行术后随访,检测其TURP术后6个月、1年的PSA值及IPSS评分,分析术后血清PSA值、IPSS的变化,评估TURP在前列腺增生伴血清PSA异常患者中的诊疗效果。结果:①40例前列腺穿刺活检阴性而血清PSA持续异常的患者中,2例术后病理示前列腺腺癌(2/40),Gleason评分为6分,另1例电切后病理示前列腺增生组织,但术后血清PSA持续异常(18μg/L),行2次活检,病理诊断为前列腺癌,Gleason评分6分,3例均行前列腺根治性切除术,术后随访恢复好。31例拒绝活检患者中术后病理示前列腺腺癌9例(9/31)。Gleason评分7⁹分,平均8分,1例行前列腺根治性切除术,8例行内分泌治疗。②59例病理诊断为良性前列腺增生(BPH),其中血清PSA恢复正常者56例,显著降低者3例,IPSS评分有明显改善53例,6例尿道狭窄经过尿扩处理后评分亦有改善。结论:诊断性TURP可提高前列腺癌的早期检出率,改善患者的下尿路症状,且有利于患者血清PSA持续正常化。对血清PSA异常(>4μg/L),伴有下尿路梗阻状态、前列腺穿刺活检阴性的患者可考虑行诊断性TURP。     

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。     

经尿道前列腺电切术治疗高龄高危前列腺增生症(附216例)

目的探讨经尿道前列腺电切术（TURP）治疗高龄高危前列腺增生症（BPH）的安全性和有效性。方法在积极进行个体化围手术期处理的基础上对216例高龄高危BPH患者行TURP术。结果本组216例安全实施TURP,手术平均时间46min,电切前列腺组织平均41g。随访6～12个月,所有患者排尿通畅,无一例水中毒、永久性尿失禁及继发性出血。国际前列腺症状评分（IPSS）由30.5分降到7.8分,剩余尿（PVR）由156ml降至20ml,最大尿流率（Qmax）由8ml/s增至20ml/s,生活质量评分（QOL）由4.9分降到1.5分,治疗前后IPSS、PVR、Qmax、QOL改变有统计学意义。结论只要加强个体化围手术期的处理,TURP仍是治疗高龄高危BPH安全有效的方法。     

五分法经尿道前列腺电切术治疗高危重度前列腺增生(附102例报告)

目的探讨经尿道前列腺五分法电切术治疗高龄、高危、重度前列腺增生患者的安全性与疗效。方法高龄高危重度BPH102例，采用前列腺五分法TURP治疗68例，常规法TURP治疗34例，对两组病例的手术时间、切除增生腺体重量、术中出血量、术中输血量、手术前后Qmax、RUV、IPSS、QOL及近期手术并发症发生率等进行比较。结果两组手术均获得成功;与常规法TURP组相比较，五分法TURP组的平均手术时间、术中出血量及输血量明显缩短或减少，而且切除腺体重量较多、近期手术并发症发生率较低，差异有统计学意义（P〈0.05）。术后3个月，五分法组与常规法组Qmax、RUV、IPSS及QOL较术前明显改善（P〈0.05），但组间无显著性差异（P〉0.05）。结论前列腺五分法TURP治疗高龄、高危、重度BPH患者与常规法TURP相比较具有手术时间短、切除增生腺体组织多、术中出血及手术并发症少等，提高了手术的安全疗效。     

High expression of PSM-E correlated with tumor grade in prostate cancer: a new alternatively spliced variant of prostate-specific membrane antigen

BACKGROUND: Prostate-specific membrane antigen (PSMA) overexpressed in prostate cancer (PCa) has been targeted for therapy and diagnosis of PCa. In the current study, PSMA cDNA was cloned from PCa tissue by RT-PCR. After sequencing, a new spliced variant of PSMA (PSM-E) was discovered and its specificity in PCa was evaluated. METHODS: PSM-E and PSMA mRNA were measured in LNCaP, PC-3 and prostate or nonprostatic malignancies. Following transfection of PC-3 with PSM-E cDNA in the pcDNA3.0 vector, PSM-E expression was measured by immunofluorescence and Western-blot. PSM-E and PSMA mRNA levels were quantified by a real-time PCR assay in normal prostate (n = 7), benign prostatic hyperplasia (BPH) (n = 22) and PCa (n = 41). The correlation between their levels and tumor grade was analyzed. RESULTS: PSM-E cDNA is identical to PSMA except for a 97-nucleotide region and a 93-nucleotide region. PSM-E and PSMA mRNA were detected in PCa and LNCaP, not in PC-3; PSMA could be detected in some nonprostatic tumors whereas PSM-E not. The expression of PSM-E protein was detected in transfected cells. Significant difference of PSM-E mRNA levels was observed among normal prostate, BPH and PCa (P < 0.001), and PSM-E levels increased with increasing Gleason score (r = 0.514, P < 0.001). PSMA mRNA levels were higher in BPH and PCa than in normal prostate (P < 0.001), but no difference between BPH and PCa, no significant correlation was observed between PSMA levels and Gleason score (r = 0.229, P = 0.057). CONCLUSIONS: PSM-E may be a potential prognostic indicator for PCa progression and may be a new target antigen for therapy of PCa.     

LC3A蛋白在前列腺癌中的表达及意义

目的:探讨LC3A蛋白在前列腺癌中的表达及意义。方法:应用免疫组化方法检测LC3A在54例前列腺癌和14例良性前列腺增生(BPH)中的表达状况。结果:LC3A蛋白阳性信号定位于细胞质和/或细胞核,在前列腺癌中胞质强阳性率为90.7%,在BPH中的胞质强阳性率为14.3%,两组差异有显著性(P0.01);并发现前列腺癌中22例核着色(40.7%),LC3A胞质表达与细胞核表达无相关性(P0.05)。LC3A表达与Gleason评分呈正相关(胞质r=0.297,P=0.029;胞核r=0.288,P=0.034)。LC3A与患者的临床分期、年龄、雄激素受体(AR)及术前患者血清PSA及结合PSA(cPSA)水平均无相关性(P0.05)。LC3A在前列腺癌及BPH组织间质中的纤维细胞及平滑肌细胞也见着色。AR在前列腺癌中阳性率为74.1%(40/54),在BPH的阳性率为64.3%(9/14)。两者阳性率差异无统计学意义。结论:LC3A可能与前列腺癌的发生、分化及预后有关。     

核干因子在前列腺癌中的表达及其临床意义

目的:探讨核干因子(NS)基因在前列腺癌组织中的表达及其临床意义。方法:利用RT-PCR及免疫组化方法对前列腺癌、良性前列腺增生(BPH)及高级别前列腺上皮内瘤(HGPIN)组织中NS基因的表达进行检测,并探讨NS蛋白表达水平与前列腺癌患者临床指标的关系。结果:前列腺癌中NSmRNA表达水平显著高于BPH中的表达水平,NS蛋白在前列腺癌中的强阳性、阳性及弱阳性表达率分别为48.8%、36.6%及12.2%,在BPH中分别为4.0%、32.0%及56.0%,在HGPIN中分别为5.0%、25.0%及60.0%,在前列腺癌中的表达水平显著高于BPH及HGPIN中的水平,具有统计学意义(P<0.05)。NS基因表达水平与前列腺癌的分化程度呈负相关,细胞分化程度越差,NS基因表达水平越高。结论:前列腺癌中高表达NS基因,NS基因在前列腺癌的不良分化和恶性增殖中可能起着重要作用。