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。     

转移抑制基因Kai1在前列腺癌中的表达

目的了解转移抑制基因Ｋａｉ１蛋白在前列腺癌（ＰＣａ）中的表达。方法采用免疫组化ＬＳＡＢ法分别测定５例正常前列腺、１０例前列腺增生症（ＢＰＨ）和３４例ＰＣａ（均为腺癌,临床Ｃ期或Ｄ期）新鲜前列腺组织中Ｋａｉ１蛋白的表达。结果Ｋａｉ１蛋白分布在腺上皮细胞膜的细胞与细胞连接部,正常前列腺和ＢＰＨ的Ｋａｉ１蛋白染色连续均匀一致,而在ＰＣａ则染色分布不连续,并且染色强度较ＢＰＨ明显降低,差异有显著性（Ｐ＜０．０１）。癌细胞Ｋａｉ１蛋白染色强度与病理分级呈负相关（Ｐ＜０．０５）,与临床分期无相关（Ｐ＞０．０５）。结论Ｋａｉ１蛋白表达下降可能预示ＰＣａ转移,成为临床判断ＰＣａ预后的分子指标。     

血小板衍生生长因子受体在前列腺良恶性病变中的表达及意义

生长因子及其受体表达失调可导致细胞增殖及恶变。为探讨血小板衍生生长因子受体（ＰＤＧＦＲ）表达与前列腺病变关系，用免疫组织化学ＳＰ法研究１４例正常前列腺（ＮＰ）、５６例前列腺增生症（ＢＰＨ）、３３例前列腺癌（ＰＣａ）组织中ＰＤＧＦＲ的表达。发现ＢＰＨ、ＰＣａ组织阳性率分别为７８６％、９３９％，明显高于正常组织的２１４％，Ｐ均＜００１。阳性染色分布于上皮、基质、血管平滑肌、炎症细胞的胞浆、胞膜及核膜。提示ＰＤＧＦＲ的高表达与ＢＰＨ、ＰＣａ和新生血管的发生、发展有密切关系，未发现ＰＤＧＦＲ的高表达在肿瘤的分期、分级中有差异。     

P53,Rb抑癌基因突变产物在前列腺癌中的表达

用Ｐ５３和Ｒｂ，通过免疫金－银染色方法，对３０例前列腺癌及２０例前列腺增生症进行检测。结果显示：前列腺癌Ｐ５３、Ｒｂｃ１５的阳性率分别为６０．０％和５０％，前列腺增生症仅有１０％和１５％，二者之间有显著性差异。前列腺正常组织阳性率Ｐ５３ 和Ｒｂ为０，与肿瘤区比较Ｐ＜０．００１；３０例前列腺癌中，有１０例Ｐ５３和Ｒｂ同为阳性，Ｐ５３在低分化和未分化癌中阳性表达明显高于高分化腺癌（Ｐ＜０．０１）。     

EGFR和ABS在前列腺增生和癌变组织中的表达及意义

为探讨前列腺增生和前列腺癌的病因及发病机制，应用免疫组织化学ＳＰ法检测了１４例正常前列腺、６０例前殓腺增生和３３例前列腺癌组织中表达生长因子受体和雄激素结合位点的表达。结果显示，前列腺增生和前列腺癌组织中ＥＣＦＲ阳性表达率明显高于正常组织；前列腺癌中ＡＢＳ的阳必明显高于增生和正常组织，而增生组织中，ＡＢＳ强阳性率又明显高于正常组织。ＥＧＦＲ表达与肿瘤病理分级呈正相关，而与ＡＢＳ表达无相关。ＥＧＦＲ     

前列腺癌组织神经内分泌细胞的免疫组化超微诊断及意义

应用透射电镜技术对４０例前列腺癌、２０例前列腺增生症及１０例正常前列腺组织的神经内分泌（ＮＥ）细胞进行观察，并与抗嗜铬粒蛋白Ａ（ＣｇＡ）、神经元特异性烯醇化酶（ＮＳＥ）和６种激素抗体免疫组化技术进行对比观察。前列腺癌中含ＮＥ型癌细胞３２例，依据内分泌颗粒的形态不同可分为三种类型，前列腺增生症ＮＥ细胞的形态与正常前列腺组织相似，但数量有明显变化。对正常前列腺组织细胞的超微形态与功能，前列腺癌中ＮＥ细胞超微诊断及临床病理意义进行了探讨     

前列腺良恶性组织中Fas及其配体FasL表达的意义

应用免疫组化方法检测正常、增生和癌变前列腺组织中Ｆａｓ和ＦａｓＬ的表达及应用ＴＵＮＥＬ方法检测细胞凋亡,探讨其意义。材料与方法　６２例前列腺增生（ＢＰＨ）,平均６４岁。３３例前列腺癌（ＰＣ）,平均６６岁。ＰＣ按Ｍｏｓｔｏｆｉ分级：高分化１０例、中分化１４例、低分化９例。按ＪｅｗｅｔｔＷｈｉｔｍｏｒｅＰｒｏｕｔ分期：Ａ期１５例、Ｂ期１４例、Ｃ期和Ｄ期各２例。１８例正常前列腺（ＮＰ）作为对照。石蜡包埋,切片厚４μｍ。免疫组化采用ＳＰ方法,Ｆａｓ（１∶１００）和ＦａｓＬ（１∶５０,抗原修复）均为兔…     

前列腺增生和癌变组织中碱性成纤维细胞生长因子的表达及其临床意义

为了探讨碱性成纤维细胞生长因子（ｂＦＧＦ）在前列腺组织中表达、分布情况及临床意义，应用免疫组化方法检测１４例正常前列腺（ＮＰ）、５６例前列腺增生症（ＢＰＨ）和３３例前列腺癌（Ｐｃａ）组织中ｂＦＧＦ的分布和表达。结果显示：ＢＰＨ中ｂＦＧＦ阳性率为６４３％，主要分布于间质细胞核，部分间质细胞浆、少数腺上皮细胞浆也见阳性染色；Ｐｃａ中ｂＦＧＦ阳性表达位于癌细胞浆，阳性率为８４８％，但ｂＦＧＦ表达强度与Ｐｃａ的病理分级、临床分期无明显关系；正常前列腺组织中ｂＦＧＦ表达均为阴性，三者之间阳性率差异有显著意义，表明ｂＦＧＦ参与ＢＰＨ、Ｐｃａ发生过程。     

前列腺癌组织中细胞外基质的免疫组织化学研究

为探讨前列腺癌（ＰＣａ）细胞的转移机制，应用免疫组织化学ＡＢＣ法在良性前列腺增生（ＢＰＨ）及ＰＣａ组织中对基膜连接蛋白（ＬＮ），胶原Ⅳ型蛋白（ＣＯＬⅣ），纤维连接蛋白（ＦＮ）等细胞外基质（ＥＣＭ）蛋白的表达进行检测，结果ＢＰＨ组织中基底膜部位ＬＮ，ＣＯＬⅣ及ＦＮ的染色呈连续线状分布，ＰＣａ组组织基底膜部位ＬＮ，ＣＯＬⅣ及ＦＮ的阳性染色呈碎片状或断线状分布。ＣＯＬⅣ在ＢＰＨ与ＰＣａ组织中的强阳性率无显著性差异（Ｐ＞０．０５）。结果提示ＥＣＭ在ＰＣａ组织中基底膜部位的明显缺失（非连续线状分布）可能是肿瘤转移的重要因素。     

前列腺增生和癌变组织中碱性成纤维细胞生长因子的表达及 …

为了探讨碱性成纤维细胞生长因子（ｂＦＧＦ）在前列腺癌组织中表达，分布民政部及临床意义，应用免疫组脂方法检测１４例正常前列腺（ＮＰ），５６你前列腺增生症（ＢＰＨ）和３３例前列腺癌（Ｐｃａ）组织中ｂＦＧＦ的分布和表达，结果显示：ＢＰＨ中ｂＦＧＦ阳性率为６４．３％，主要分布于间质细胞核，部分间质细胞浆，少数腺上皮细胞浆也见阳性染色，Ｐｃａ中ｂＦＧＦ阳性表达位于癌细胞浆，阳性率为８４．８％，但ｂＦＧＦ表达     

前列腺特异性膜抗原表达的临床意义

目的 探讨前列腺特异性膜抗原(PSMA)在前列腺癌(PCa)组织中的表达及与肿瘤病理分级之间的关系。方法 采用免疫组化ABC法，用PSMA单克隆抗体对前列腺不同病变组织及非前列腺肿瘤组织石蜡包埋切片进行染色。其中PCa 70例，前列腺上皮肉瘤21例，良性前列腺增生20例．其他肿瘤组织标本30例。结果 PSMA在97％前列腺癌、100％前列腺上皮内瘤、80％BPH组织中呈不同程度的阳性表达，且在PCa组织中呈明显高表达，非前列腺肿瘤组织染色均呈阴性。组织 PSMA表达与PCa组织学分级之间存在负相关性。结论 PSMA具有良好的组织器官特异性，能够判断PCa顶后，在PCa的免疫治疗方面具有应用前景。     

抗前列腺特异膜抗原单克隆抗体的制备及鉴定

目的 制备具有良好器官特异性的抗前列腺特异膜抗原（ＰＳＭ）单克隆抗体。方法 以前列腺癌细胞株ＬＮＣａｐ为免疫原,采用环磷酰胺免疫抑制法免疫小鼠,经细胞融合、选择性培养、筛选、克隆化等过程建立了抗ＰＳＭ的杂交瘤细胞株,并采用活细胞间接免疫荧光染色、ＥｎＶｉｓｏｎ＾ＴＭ两步法免疫组化染色、Ｗｅｓｔｅｒｎ ｂｌｏｔ对其特异性进行鉴定;双向琼脂扩散法鉴定单抗的亚类。结果 该单抗权与ＬＮＣａｐ及前列腺细胞膜     

前列腺癌组织中前列腺跨膜上皮抗原表达的临床意义

目的 :探讨前列腺跨膜上皮抗原 (STEAP)在前列腺癌 (PCa)组织中的表达及与肿瘤病理分级之间的关系。方法 :采用免疫组化SP法 ,用STEAP单克隆抗体对前列腺不同病变组织及非前列腺肿瘤组织石蜡包埋切片进行免疫组化染色 ,其中PCa组织 131例 ,良性前列腺增生 (BPH)组织 16 4例 ,非前列腺肿瘤组织标本 5 6例。引入阳性面积单位概念判定STEAP染色强度。　结果 :2 95例前列腺病变组织中 ,仅 3例PCa和 5例BPH组织STEAP呈阴性表达 ,STEAP在PCa组织中明显高表达 ,非前列腺肿瘤组织染色均呈阴性。STEAP表达与PCa的Gleason分级之间存在显著负相关性。　结论 :STEAP能够用来判断PCa的预后 ,在PCa的免疫治疗方面具有良好的应用前景。     

P504S immunohistochemical detection in 405 prostatic specimens including 376 18-gauge needle biopsies

P504S is a recently described, prostate cancer-specific gene that encodes a protein involved in the beta-oxidation of branched chain fatty acids. A recent study has shown that immunohistochemical detection of P504S gene product is a sensitive and specific marker of prostatic carcinoma in formalin-fixed, paraffin-embedded tissues. We performed a detailed analysis of P504S protein expression in a large series of prostate and bladder specimens with special emphasis on staining in specific morphologic patterns of prostatic adenocarcinoma, posthormonal and radiation therapy cases, and invasive urothelial carcinoma. A total of 366 prostate needle core biopsies from 124 patients with prostate cancer, 10 biopsies from 2 patients without prostate cancer, 28 prostatectomy specimens (16 with specific morphologic patterns, 7 posthormonal therapy and 5 postradiation therapy specimens), 5 bladder specimens with invasive urothelial carcinoma, and a single transurethral resection specimen from a patient with hormonally treated prostate cancer and invasive urothelial carcinoma were stained with P504S monoclonal antibody at a 1:250 dilution using standard heat-induced epitope retrieval and avidin-biotin technique. Extent (0, no staining; 1+, 1-10% staining; 2+, 11-50% staining; 3+, > or =51% staining) and location (luminal, subluminal, and diffuse cytoplasmic) of immunoreactivity in carcinoma and benign tissues were recorded. A total of 153 of 186 biopsies (82%) with prostatic adenocarcinoma stained for P504S. Pseudohyperplastic, atrophic, ductal, and mucinous prostatic carcinomas stained similarly, as did cases treated with hormone or radiotherapy. In 81 of 377 (21%) foci of benign prostatic tissue there was staining that was almost always focal, faint, and noncircumferential. Seminal vesicles did not stain for P504S. Five of six (83%) specimens with invasive urothelial carcinoma had 2+ staining and one case had focal staining. We conclude that immunohistochemistry for P504S has potential utility in the diagnosis of prostate cancer, including those treated by hormones and radiation. Circumferential luminal to subluminal and diffuse cytoplasmic staining is the most specific staining pattern for prostatic carcinoma and is almost never associated with benign prostatic tissue. However, a negative P504S immunostain does not automatically rule out prostate cancer, as 18% of cases were negative. Additionally, occasional benign glands, high-grade prostatic intraepithelial neoplasia, atypical adenomatous hyperplasia, and urothelial carcinoma may express P504S. Therefore, we think that P504S is best used only in conjunction with strict light microscopic correlation and preferably with high molecular weight cytokeratin immunostaining.     

Placental S100 (S100P) and GATA3: markers for transitional epithelium and urothelial carcinoma discovered by complementary DNA microarray

The morphologic distinction between prostate and urothelial carcinoma can be difficult. To identify novel diagnostic markers that may aid in the differential diagnosis of prostate versus urothelial carcinoma, we analyzed expression patterns in prostate and bladder cancer tissues using complementary DNA microarrays. Together with our prior studies on renal neoplasms and normal kidney, these studies suggested that the gene for placental S100 (S100P) is specifically expressed in benign and malignant urothelial cells. Using tissue microarrays, a polyclonal antiserum against S100P protein stained 86% of 295 urothelial carcinomas while only 3% of 260 prostatic adenocarcinomas and 1% of 133 renal cell carcinomas stained. A commercially available monoclonal antibody against S100P stained 78% of 300 urothelial carcinomas while only 2% of 256 prostatic adenocarcinomas and none of 137 renal cell carcinomas stained. A second gene, GATA3, also showed high level expression in urothelial tumors by cDNA array. A commercially available monoclonal antibody against GATA3 stained 67% of 308 urothelial carcinomas, but none of the prostate or renal carcinomas. For comparison, staining was also performed for p63 and cytokeratin 5/6. p63 stained 87% of urothelial carcinomas whereas CK5/6 stained 54%. Importantly, when S100P and p63 were combined 95% of urothelial carcinomas were labeled by one or both markers. We conclude that the detection of S100P and GATA3 protein expression may help distinguish urothelial carcinomas from other genitourinary neoplasms that enter into the differential diagnosis.     

前列腺特异性膜抗原和前列腺特异性抗原在前列腺癌组织中的表达

目的：观察并比较前列腺特异性膜抗原（PSMA）和前列腺特异性抗原（PSA）在不同前列腺为组织中的表达差异；比较组织PSMA与PSA对前列腺癌诊断和鉴别诊断的意义。方法：采用ABC三步法免疫组织化学染色方法，用PSMA和PSA单克隆抗体对70例前列腺癌（PCA）、21例前列腺上皮内瘤（PIN）、20例前列腺良性增生（BPH）组织进行染色。结果：PSMA在前列腺癌组织中明显高表达，PSA则在前列腺良性增生组织中高表达；组织PSMA对前列腺癌的阳性检出率明显高于PSA。结论：PSMA是较PSA更具特异性的前列腺癌瘤标，可望取代PSA成为诊断前列腺癌的新型瘤标，并在前列腺癌免疫治疗方面具有良好的应用前景。     

PSMA expression in Schwannoma: a potential clinical mimicker of metastatic prostate carcinoma

ObjectivesRadioimmunoscintigraphy using a radiolabeled antibody against prostate-specific membrane antigen (PSMA) is frequently used to detect prostate carcinoma (PCa) recurrence and metastasis to lymph nodes, soft tissues, and bone. PSMA expression has been shown in occasional nonprostatic neoplasms (e.g., urothelial adenocarcinoma) and in the vasculatures of other malignancies. PSMA expression has not been described in benign neoplasms. Recently, during evaluation of a prostatic carcinoma patient, we encountered a false positive PSMA radioimmunoscintigraphy scan in a pathologically confirmed Schwannoma (SCH) lesion. The current study further evaluates PSMA expression in Schwannomas.MethodsEleven SCH were retrieved from our surgical pathology archives. Representative sections were immunostained with monoclonal antibody for PSMA. PSMA expression was evaluated in tumor cells and lesional vessels. Extent of staining was calculated as percent of positive cells in highest areas of expression. Positive staining was considered focal, multifocal, or diffuse based on the percent of positive cells: <5%, 5% to 75%, and >75%, respectively.ResultsAll 11 SCH showed tumoral and or vascular staining; 7 (7/11) displayed both vascular and tumoral cell staining; the remaining 4 had only vascular staining (2/11) or tumor cell staining (2/11). The extent of tumoral cell and vascular staining varied widely among lesions (tumor cells: focal in 8 and diffuse in 1; vascular: focal in 7, multifocal in 1, and diffuse in 1 lesion).ConclusionThis is the first report of PSMA expression in a benign neoplasm. Given our finding of frequent expression of PSMA in Schwannomas, they should be clinically considered in the differential diagnosis of a lesion that is positive on PSMA radioimmunoscintigraphy study performed during a metastatic work-up of PCa patient.     

Distribution of prostasomes in neoplastic epithelial prostate cells

BACKGROUND: Prostasomes are a secretory product from the prostate. We aimed to investigate whether the distribution and amount of prostasomes in normal prostate epithelium were influenced by the dedifferentiation occurring in adenocarcinomas of the human prostate gland. METHODS: Transurethrally resected material from 11 patients with prostatic carcinoma of various malignancy grades, material from two lymph node metastases, and benign tissue from 10 total prostatectomies were subjected to immunohistochemical staining, using a mouse monoclonal antibody against human prostasomes (mAb78). RESULTS: Immunostaining of low-grade carcinoma was similar to that of normal prostate gland which displayed a cytoplasmic granular staining of the apical (luminal) aspects of the secretory epithelial cells. In moderately well and poorly differentiated adenocarcinoma, the amount of stained components decreased, and the staining pattern became more heterogeneous. In multilayered glandular structures, the staining was concentrated at the lumen, leaving most other cells negative. The neoplastic cells of lymph node metastases of prostate carcinoma differed in amount and distribution of immunostained prostasomes. CONCLUSIONS: The antigen recognized in the prostasomes by mAb78 was expressed in benign prostate tissue, prostate cancer, and to a lesser degree in lymph node metastases. There was a tendency towards decreased expression with increasing tumor grade.     

前列腺癌组织中热休克蛋白90a的表达及意义

目的 研究热休克蛋白90a(HSP90a)在人前列腺癌组织中的表达,并初步探讨其与肿瘤生物学行为的关系.方法 采用免疫组织化学方法检测了10例正常前列腺组织、15例良性前列腺增生(BPH)组织及37例前列腺癌组织中HSP90a的表达.37例前列腺癌中高、中、低分化者分别10例、12例、15例.结果 正常前列腺组织、BPH组织和前列腺癌组织中均可见HsPgoa表达,HSP90a的分布在三种组织中无差别,均于腺上皮细胞表达,基质无着色.HSP90a在正常前列腺组织、BPH组织以及高、中、低不同分化前列腺癌中表达强度的平均灰度值分别为71±7、74 ±6、142±8、145 ±7、144 ±7.正常前列腺组织和BPH组织间表达强度差异无统计学意义(P>0.05),前列腺癌组织中HsPgOa表达显著增强,与之差异均有统计学意义(P<0.05),但前列腺癌高、中、低分化组织间HSP90a表达强度差异无统计学意义(P>0.05).结论 HsPgoa在前列腺癌中的高表达在前列腺癌的发生发展中起促进作用,尚不能作为判断肿瘤恶性程度及其预后的指标.     

Syndecan‐1 expression in prostate cancer and its value as biomarker for disease progression

OBJECTIVE

To evaluate the association between syndecan‐1 (CD138) expression and prostate cancer.

PATIENTS AND METHODS

We evaluated syndecan‐1 expression using a recently constructed tissue microarray of prostatic samples taken from 243 patients, corresponding to 1400 cores, with 69.8%, 5.6%, 17.6% and 7% of the cores representing localized prostate cancer, high‐grade prostatic intraepithelial neoplasia, benign prostate tissue and hormone refractory/metastatic disease, respectively.

RESULTS

Metastatic cases had the highest frequency and membranous staining intensity for syndecan‐1 overexpression, followed by hormone refractory and localized disease (83.3% vs 34.8% and 25.7%, respectively). There was no significant difference in the frequency of membranous syndecan‐1 expression between localized prostate cancer and benign glands (25.7% vs 24.7% of cases, respectively). However, benign glands showed significantly higher intensity staining than localized prostate cancer. We found no significant association between syndecan‐1 expression and any of the following: Gleason score, pathological stage, surgical margin status and biochemical recurrence.

CONCLUSION

The current available evidence, from the present and previous studies, show that syndecan‐1 is not an independent predictor of recurrence or tumour‐specific survival, diminishing its significance as a clinical marker.