前列腺组织端粒酶活性检测对前列腺癌的诊断价值

目的 通过检测前列腺穿刺组织端粒酶活性,探讨其在前列腺癌诊断和预后中的临床价值。方法 ２０例前列腺癌标本和１６例癌旁组织均来自前列腺穿刺活检,１４例良隆前列腺增生（ＢＰＨ）标本取自前列腺摘除手术,均经病理证实。采用改良的ＴＲＡＰ－银染方法检测端粒酶活性,并进行半定量分析。结果 ２０例前列腺癌标本中１８例测得端粒酶活性。１６例前列腺癌旁组织中,７例前列腺上皮内瘤（ＰＩＮ）,２例癌旁ＢＰＨ组织有端粒酶     

前列腺穿刺物端粒酶活性测定对前列腺癌的诊断价值

目的：通过检测前列腺穿刺物端粒酶活性，探讨其在前列腺癌诊断中的价值。方法：对41例可疑前列腺癌患者进行前列腺穿刺，对穿刺物行端粒酶活性测定及病理检查。端粒酶活性采用端粒重复放大程序（TRAP）PCR银染色法作定性检查，同时采用TRAP－PCR ELISA法作半定量测定。结果：26例前列腺癌患者中，端凿酶活性检测阳性22例，阳性率为84．6％，平均活性值为0．4506；15例非前列腺癌患者中，阳性4例，阳性率为26．7％，平均活性值为0．1263。两组之间端粒酶表达率及活性值差异均有显著性意义（P＜0．05或P＜0．01）；癌旁组织17例，阳性2例（11．8％）。前列腺癌端粒酶活性表达与肿瘤分级、分期及术前血清前列腺特异抗原无关（P＞0．05）。结论：前列腺穿刺物端粒酶活性测定是一种诊断前列腺癌的有用标志。     

前列腺活检组织α-甲酰基辅酶A消旋酶检测的临床意义

目的探讨超声引导下经会阴前列腺细针密集穿刺组织中α-甲酰基辅酶A消旋酶(P504S)检测的应用价值。方法对170例超声引导下经会阴前列腺穿刺组织进行相关病理检测,诊断为前列腺癌65例(38．2％)、良性前列腺增生(BPH)97例(57．1％)、前列腺上皮内瘤(PIN) 5例(2．9％)、不典型小腺体增生(ASAP)3例(1．8％)。传统6针穿刺法获得的40例前列腺组织中8例(20．0％)病理诊断为前列腺癌。免疫组织化学法检测其P504S表达情况。结果超声引导下经会阴穿刺组65例前列腺癌组织P504S阳性表达率为100．0％,其中弥漫阳性(≥ )表达者64例(98．5％);97例BPH组织中P504S表达( )者16例(16．5％),( )者1例(1．0％),阴性者80例(82．5％);5例PIN和3例ASAP组织中P504S均为阴性表达。经直肠6针穿刺的8例前列腺癌组织标本P504S染色均呈弥漫阳性。超声引导下经会阴穿刺组和传统6针穿剌组中前列腺癌检出率差异有统计学意义(P<0．05),但2组前列腺癌组织中P504S阳性率差异无统计学意义(P> 0．05)。结论P504S可作为前列腺癌的肿瘤标记物,在前列腺穿刺活检组织病理诊断中有一定辅助诊断价值。     

端粒酶活性在人膀胱肿瘤组织中表达的临床意义

目的：探讨不同临床病理类型的膀胱肿瘤及癌旁组织端粒酶活性表达及临床意义，方法：以改良TRAP法测定91例膀胱肿瘤组织标本端粒酶活性表达。结果：83例膀胱移行细胞癌组织中78例检测到端粒酶活性，阳性率为94％，其对应的癌旁组织也有14％的检出率，8例膀胱乳头状瘤组织中4例检测到端粒酶活性，阳性率为50％，其对应的癌旁组织检出率为12％，端粒酶活性在不同临床病理类型的膀胱肿瘤及癌旁组织中表达差异无显著性意义（P＞0．05），结论：膀胱肿瘤及癌旁组织端粒酶活性的检测对肿瘤的诊断有重要意义。     

膀胱癌癌旁组织端粒酶活性检测的临床意义

目的　探讨膀胱癌癌旁组织端粒酶活性检测的临床意义。　方法　采用端粒重复序列扩增 (TRAP)法 ,检测 2 4例膀胱癌组织及癌旁组织中端粒酶活性表达。　结果　 2 4例癌旁组织中端粒酶活性表达阳性 10例 (42 % ) ,癌旁组织端粒酶活性表达与原发灶癌病理分级分期相关 ,并与癌复发相关。　结论　膀胱癌癌旁组织端粒酶活性检测可作为判断膀胱癌预后的指标之一     

应用端粒酶活性检测前列腺按摩后前列腺癌细胞

作者建立并评估了一种诊断前列腺癌的非侵袭性方法 ,此方法基于检测前列腺按摩后新鲜尿液或尿道冲洗液的端粒酶活性。 36份前列腺按摩后的细胞标本 ,其中 16例标本来自新鲜尿液 ,且这些患者随后进行了前列腺根治性切除术 ,另 2 0例标本来自尿道冲洗液 ,这些患者进行了前列腺针吸活检。在收集的尿液或冲洗液中立即加入乙二胺四乙酸(ＥＤＴＡ) ,终浓度为 2 0ｍｍｏｌ/Ｌ。标本经ＣＨＡＰＳ缓冲液提取蛋白质后 ,应用改良的端粒酶 2步重复扩增法检测端粒酶活性。具有高端粒酶活性的前列腺癌细胞系ＰＣ 1和ＬＮＣａＰ作为阳性对照。结果发现 ,在…     

细针穿刺标本中端粒酶活性检测对甲状腺癌的诊断

目的　探讨甲状腺肿块细针穿刺活检 (FNAB )标本中端粒酶活性检测在甲状腺癌术前诊断中的应用价值。方法　在超声引导下穿刺抽取甲状腺组织FNAB标本 ,分别进行细胞学病理检查和端粒酶活性检测。以术后石蜡病理切片结果为最终标准 ,对以上两者结果进行对照、分析。结果　在 3 2例甲状腺癌中 ,FNAB的正确诊断率为 43 .8%(14 /3 2 ) ,端粒酶活性阳性率为 75 .0 %(2 4/3 2 ) ,两者相比有显著差异 (P <0 .0 5 )。在 18例甲状腺癌被FNAB诊断为“可疑阳性”、“取材不够”、“阴性”及“甲状腺炎”者中 ,14例显示端粒酶活性 ,阳性率为 77.8%(14 /18)。两者联合诊断率可提高至 87.5 %。结论　端粒酶活性检测是FNAB很好的辅助诊断方法 ,两者联合应用可明显提高FNAB标本的阳性诊断率。     

端粒酶活性表达与老年肾癌生物学特性的关系

目的 研究端粒梅活性表达与老年肾癌(RCC)生物学行为的关系。方法 应用改良的端粒重复片段扩增法(TRAP法)检测24例老年RCC组织、癌旁组织及正常肾组织中端粒酶活性,并探讨端粒酶活性表达与RCC生物学特征的关系。结果 RCC组织中端粒酶表达阳性率为87.5％,显著高于癌旁组织(20％)及正常肾组织(5％),差异显著(P<0.01),端粒酶活性表达与RCC细胞类型、分级、分期无关,与肿瘤大小、DNA含量相关。结论 RCC组织中端粒酶激活与肾癌的发生有关,端粒酶活性检测有可能成为RCC早期诊断、治疗及预后判断的重要指标。     

前列腺衰老逃逸现象的实验研究

目的探讨良性前列腺增生(BPH)衰老逃逸现象的机理。方法采用端粒重复片段扩增法(TRAP)分别检测13例正常前列腺组织、35例BPH组织及33例增生结节和包膜的端粒酶活性表达情况,比较端粒酶活性水平与BPH衰老逃逸的关系。结果正常前列腺组织中端粒酶阳性2例(15%),BPH组织中端粒酶阳性17例(49%),增生结节端粒酶阳性14例(42%),包膜阳性1例(3%);BPH组织端粒酶阳性表达率高于正常前列腺组织(P<0.05),增生结节阳性率明显高于包膜组织(P<0.01)。结论BPH组织中端粒酶活性升高,且分布不均匀。提示前列腺衰老逃逸可能与端粒酶活性有关。     

α-甲基-辅酶A消旋酶在前列腺癌中的表达及意义

目的　探讨α 甲基 辅酶A消旋酶 (P5 0 4S)表达在国人前列腺癌病理诊断中的价值。　方法　对 4 2例前列腺癌、18例前列腺上皮内瘤 (PIN)和 2 5例良性前列腺增生 (BPH)标本进行P5 0 4S、高分子质量角蛋白 (34βE12 )和血管内皮生长因子 (VEGF)免疫组化染色 ,观察比较分析染色范围和强度。　结果　前列腺癌标本P5 0 4S染色阳性 33例 (79% ) ,染色强度为中等到强阳 ,明显高于BPH和PIN ,癌旁组织均为阴性 ;6例 (33% )PIN标本 ,2例 (8% )BPH标本有少量细胞微弱表达 ,其余均为阴性。BPH标本具有完整基底层细胞 ,34βE12 呈阳性表达 ;PIN腺体基底层细胞 34βE12 表达阳性 ,相对BPH强度减弱 ;4 0例前列腺癌腺体无基底层细胞 ,仅 2例有不完整的基底层呈弱表达。BPH、PIN和前列腺癌标本VEGF均呈阳性表达 ,各组阳性细胞数和染色强度相差不明显。　结论　P5 0 4S诊断前列腺癌敏感性高、特异性好 ,结合 34βE12 检测可提高前列腺癌的检出率。     

端粒酶与前列腺癌及其生物学行为的关系

目的 探讨端粒酶（ＴＥ）与前列腺癌（ＰＣａ）及其生物学行为的关系。方法 应用端粒重复片段扩增法（ＴＲＡＰ）法,检测３９例ＰＣａ组织,１５例前列腺增生（ＢＰＨ）组织及１０例正常前列腺（ＮＰ）组织中的ＴＥ活性,并比较ＴＥ活性水平与ＰＣａ病理分化程度,临床分期及转移情况的关系。     

An appraisal of telomerase activity in benign prostatic hyperplasia

BACKGROUND: Prostate cancer is one of the commonest neoplasms in elderly males in developed countries. It is not clear which individuals are at high risk of developing aggressive adenocarcinoma of the prostate. Biomarkers are therefore urgently needed to identify such individuals. It had been suggested both by ourselves and others that prostatic telomerase activity may represent a valuable marker in this respect, particularly if applied to BPH, as tissue is readily available from both transurethral resection of prostates and transrectal ultrasound biopsy. METHODS: Tissue was collected prospectively from 46 patients with BPH who underwent TURP for clinically benign prostatic disease, and who were examined using the telomeric repeat amplification protocol (TRAP assay). RESULTS: Telomerase activity was not detected in any of 46 BPH samples, using TRAP assay conditions of 0.12, 1.2, and 12.0 microg protein. CONCLUSIONS: The study confirms that telomerase is not detectable in BPH samples. This would suggest that absence of telomerase activity may be a strong indicator of a lack of cancer. However further studies are necessary to confirm this.     

FOCAL INTRATUMORAL HETEROGENEITY FOR TELOMERASE ACTIVITY IN HUMAN PROSTATE CANCER

PURPOSE: The value of telomerase activity as a marker in clinical decision-making is closely related to how representative the analysis of a small tumor sample is for the whole tumor. We therefore evaluated the intratumoral distribution pattern of telomerase activity in prostatic carcinomas. MATERIALS AND METHODS: From 50 prostate cancer patients treated with radical prostatectomy, telomerase activity was determined using the telomeric repeat amplification protocol (TRAP assay). Comparative analysis of at least two separate cancer areas from a single tumor was performed in 42 cases. RESULTS: Telomerase activation has been demonstrated in 90% of the prostatic carcinomas. Focal intratumoral heterogeneity was found in 38.1% of the tumors with at least two different areas examined. Telomerase positivity of all samples from one given tumor was detected in 50%, telomerase negativity of all samples in 11.9%. A heterogeneous telomerase activity pattern was more frequently detected in tumors with a Gleason score < or = 7 than in those with a Gleason score > 7. Furthermore, there was an increase in the proportion of homogeneously telomerase-positive tumors with increase in severity of the Gleason score. The differences reached statistical significance. Telomerase activity was also detected in non-cancerous prostatic tissue samples. CONCLUSIONS: Telomerase activation is nearly ubiquitous in prostatic carcinomas, although a heterogeneous telomerase activity pattern within tumors might produce a false-negative result in the telomerase activity assay. This limits the value of telomerase activity assays for diagnostic means. There is evidence for a shift from telomerase-negative prostate cancer tissue toward telomerase positivity during the progression process of prostate cancer. The relatively high proportion of telomerase-positive nonmalignant prostatic tissue samples argues against cancer-specificity of telomerase activation.     

IMPDH2蛋白与前列腺癌临床相关性分析

【摘要】〓目的〓研究IMPDH2在良性前列腺增生和前列腺癌中的表达,并分析其表达水平与临床病理特征的关系。方法〓收集临床手术切除的前列腺癌组织和前列腺增生,或者穿刺活检组织,所有组织均由病理学确诊。排除已做手术去势的前列腺组织。通过Western Blot检测IMPDH2在前列腺癌、前列腺增生组织中IMPDH2蛋白的表达情况|免疫组化检测前列腺癌、前列腺增生标本中IMPDH2的表达。分析IMPDH2基因的表达水平与临床病理特征的关系。结果〓前列腺癌患者组织中IMPDH2蛋白表达显著上调,IMPDH2蛋白表达上调与肿瘤临床分期、Gleason评分、转移相关。结论 IMPDH2在前列腺癌组织中表达上调,前列腺组织中检测IMPDH2可能有助于判断前列腺癌分化程度并评估预后。     

The use of telomerase activity for the detection of prostatic cancer cells after prostatic massage

PURPOSE: Prostate cancer is the most commonly diagnosed cancer in the United States. The diagnosis or followup of prostate cancer in men older than 50 years is based on digital rectal examination, measurement of the free-to-total prostatic specific antigen ratio and transrectal ultrasound assisted needle biopsy of the prostate. We developed and evaluated a noninvasive method for diagnosing prostate cancer based on the measurement of telomerase activity after prostatic massage in fresh voided urine or after urethral washing. MATERIALS AND METHODS: We obtained 36 specimens of cells after prostatic massage in the fresh voided urine of 16 patients who subsequently underwent radical prostatectomy and after urethral washing in 20 who underwent prostate needle biopsies. Ethylenediaminetetraacetic acid was immediately added to the collected urine or washing to a final concentration of 20 mM. After protein extraction by CHAPS buffer each specimen was tested for telomerase activity in a 2-step modified telomeric repeat amplification protocol assay. The 2 prostate cancer cell lines PC-3 and LNCaP with high telomerase activity were used as a positive control. RESULTS: Telomerase activity was detected in 14 of 24 samples with known prostate cancer (sensitivity 58%). In contrast, no telomerase activity was found in the 12 cases without histological evidence of prostate tumor (specificity 100%). Eight of 9 poorly differentiated cancers expressed telomerase activity (89%), while only 6 of 15 well and moderately differentiated cancers showed telomerase activity (40%). CONCLUSIONS: Our data illustrate that telomerase activity may be detected in voided urine or washing after prostatic massage in patients with prostate cancer. Sensitivity was higher for poorly differentiated tumors. This approach is not currently available for detecting prostate cancer in clinical practice. However, these results are promising and further studies are ongoing.     

Telomerase activity in prostate sextant needle cores from radical prostatectomy specimens

Human telomerase acts to maintain functioning telomeres, which are required for cellular immortality and very likely for cancer progression. Telomerase activity is present in about 85% of human cancers tested, but it has not been found in most human somatic cells and tissues. We used the Telomeric Repeat Amplification Protocol to perform telomerase activity assays on sextant needle core samples obtained from 35 freshly excised radical retropubic prostatectomy specimens. Similar assays were done on prostatic tissues obtained by means of other urologic procedures from 8 patients without prostate cancer. Telomerase activity was found in one or more specimens from 32 of 35 prostate cancer patients (91%), but was not detectable in all biopsy specimens from 7 of 8 cancer-free patients (88%). Further analysis showed that cancers more poorly differentiated, with higher Gleason scores, were always associated with a higher rate of telomerase detection and stronger telomerase activity. Moreover, comparison of telomerase activity in needle core samples with the volume of cancer in surrounding tissue as observed on corresponding histologic slides showed that stronger activity was positively correlated with a higher cancer volume. Prognostic indicators of prostate cancer and the expression of telomerase appear to be linked. The presence of telomerase activity in prostate tissue may aid in the detection of prostate cancer and produce additional prognostic information.     

Prostate-specific membrane antigen (PSMA) enzyme activity is elevated in prostate cancer cells

BACKGROUND: Prostate-specific membrane antigen (PSMA) is a glutamate carboxypeptidase that cleaves terminal carboxy glutamates from both the neuronal dipeptide N-acetylaspartylglutamate (NAAG) and gamma-linked folate polyglutamate. The prostate enzyme has activity in both the membrane and cytosolic fractions termed PSMA and PSMA', respectively. METHODS: Using a NAAG hydrolytic radioenzymatic assay, we quantitated the enzymatic activity of PSMA and PSMA' in normal, benign prostatic hyperplasia (BPH), and prostate cancer (PC) tissues from radical prostatectomies. PSMA enzyme activity was evaluated in each tissue type and expressed per milligram protein and epithelial cell content. RESULTS: PSMA and PSMA' enzyme activities were significantly elevated in prostate cancer when compared to normal prostate tissue and BPH. Ratios of PSMA to PSMA' were also decreased in BPH as compared to cancerous and normal tissue. CONCLUSIONS: Prostate carcinogenesis is associated with an elevation in PSMA and PSMA' enzyme activity. In contrast, no such enhancement in PSMA activity is observed with benign neoplastic changes in BPH. Thus, the enhancement observed in prostate cancer is not simply related to a generalized prostatic hyperplasia, but is specific to its malignancy.