聚集素在前列腺正常、增生、癌组织中的表达及意义

目的　通过检测聚集素 (Clusterin)在前列腺正常、增生、癌变组织中的表达 ,探讨其与前列腺疾病发生发展的关系。　方法　采用免疫组织化学染色法检测 12例正常前列腺组织、15例良性前列腺增生组织 (BPH)、5 6例前列腺癌标本中Clusterin的表达水平。　结果　 3种组织中Clusterin的阳性及弱阳性表达率为 81% (67/83 ) ,其中前列腺正常、增生、癌组织中阳性及弱阳性表达率分别为17% (2 /12 )、73 % (11/15 )、96% (5 4/5 6)。前列腺癌组织中Clusterin表达水平明显高于前列腺正常 (t=8 82 ,P <0 0 1)及增生 (t =7 63 ,P <0 0 1)组织 ,且在癌组织中与肿瘤病理分级 (r =0 64 9,P <0 0 1)、临床分期 (r=0 60 9,P <0 0 1)呈正相关。　结论　Clusterin可能通过抗凋亡机制在前列腺癌的生物特性中发挥着重要的作用     

TRAIL受体在前列腺癌中的表达

目的　探讨肿瘤坏死因子相关诱导凋亡配体 (TRAIL)受体在前列腺癌组织中的表达及其与前列腺癌恶性度的关系。方法　采用免疫组织化学方法检测前列腺癌组织及良性前列腺增生组织中DR4、DR5及DcR1的表达。结果　前列腺癌组织DcR1表达水平显著低于良性前列腺增生组织 (P <0 .0 1) ,DR4、DR5的表达水平两者无显著性差异。前列腺癌组织中DR4、DR5及DcR1的表达程度与前列腺癌组织的病理分级和临床分期无关 (P >0 .0 5 )。结论　TRAIL基因受体DcR1在前列腺癌凋亡机制中可能发挥重要作用     

前列腺癌血清PSAD与原位PSA的相关性研究

目的 :探讨前列腺癌患者血清前列腺特异抗原密度 (PSAD)与组织原位PSA表达的关系。方法 :参照Gleason标准对 2 5例前列腺腺癌组织进行分级 ,用免疫组织化学SP法检测前列腺癌组织中PSA ,术前 1周用化学发光分析法测定血清PSA浓度及经腹B超测定前列腺体积 ,二者之比为PSAD。结果 :5例高分化肿瘤全部呈强阳性 ;13例中分化肿瘤中 ,4例呈强阳性 ,9例呈弱阳性 ;7例低分化肿瘤中 ,1例呈强阳性 ,3例呈弱阳性 ,3例阴性。 2 5例腺癌PSAD为 0 .36～ 1.5 3(U =0 .75 )。不同分化的癌组织的PSA表达强度差异有显著性意义(P <0 .0 5 ) ,高、中分化组的血PSAD与低分化组差异有显著性意义 (P <0 .0 5 ) ,不同PSA表达强度的患者血PSAD差异无显著性意义 (P >0 .0 5 )。结论 :癌组织中蛋白酶的破坏造成PSA漏出增多 ,可能与血PSAD升高有关。癌组织PSA的免疫组织化学反应强度不能用于解释血PSAD的变化     

前列腺癌细胞凋亡与iNOS、Bcl-2的表达及意义

目的 :探讨细胞凋亡和诱生型一氧化氮合酶 (iNOS)、Bcl 2蛋白表达在前列腺癌中的意义以及两者之间的关系。　方法 :对 2 4例前列腺癌、15例前列腺增生及 5例正常前列腺组织行原位细胞凋亡检测及iNOS、Bcl 2蛋白免疫组化检测。　结果 :前列腺癌组的细胞凋亡率和iNOS的染色强度均显著高于前列腺增生组及正常前列腺组(P <0 .0 1) ,且Bcl 2蛋白表达阳性者的细胞凋亡率显著低于阴性者 (P <0 .0 1)。　结论 :前列腺癌的细胞凋亡率可反映其恶性程度 ;iNOS的表达与前列腺癌的分化程度无关 ,但与Bcl 2蛋白表达呈负相关 ;Bcl 2蛋白表达与前列腺癌细胞凋亡呈负相关。iNOS与Bcl 2均可通过影响前列腺癌细胞凋亡而在前列腺癌病理发生发展中起作用     

细胞因子通路抑制因子3在前列腺癌中的表达及其意义

目的 检测细胞因子通路抑制因子3( SOCS3)在前列腺癌和前列腺增生组织中的表达,分析其表达水平与临床病理参数的关系,探讨SOCS3在前列腺癌中的意义.方法 通过实时荧光定量聚合酶链反应(RT-qPCR)检测SOCS3基因在前列腺癌、前列腺增生组织中的表达,免疫组织化学技术检测前列腺癌、前列腺增生组织中SOCS3蛋白的表达,结合SOCS3免疫组织化学评分与前列腺癌患者临床病理参数进行分析.结果 相对于前列腺增生组织,前列腺癌患者组织中SOCS3表达下调(P＜0.01);49例前列腺癌组织有26例阳性,29例前列腺增生组织有22例染色阳性,SOCS3在前列腺增生组织的染色强于前列腺癌组织(P＜0.05);SOCS3表达与前列腺癌患者血清前列腺特异性抗原(PSA)水平(P＜0.01)、Gleason评分(P＜0.05)和肿瘤TNM分期呈负相关(P＜0.01),与肿瘤转移呈正相关(P＜0.01),与年龄无明显相关(P＞0.05).结论 检测SOCS3可鉴别前列腺癌和前列腺增生;在前列腺癌中SOCS3表达下调可抑制前列腺癌的进展,表达上调促进前列 腺癌转移.     

PARP-1及其活性产物PAR在人前列腺癌组织中的表达及意义

目的探讨多聚（腺苷二磷酸核糖）聚合酶[Poly（ADP—ribose）polymerases,PARP]亚型PARP1及其活性产物聚腺苷二磷酸核糖[Poly（ADP—ribose）,PAR]在前列腺增生和前列腺癌组织中的表达及意义。方法应用免疫组织化学SP法检测并比较PARP1和PAR在19例前列腺增生和38例前列腺癌组织中的表达,及其在高分化前列腺癌（Gleason评分≤6分）和低分化前列腺癌（Gleason评分≥9分）组织中的表达差异。结果与前列腺增生相比,PARP-1和PAR在前列腺癌组织中的表达阳性率均明显升高,差异有统计学意义（P〈0．05）;虽然在高分化与低分化前列腺癌组织中的表达阳性率无明显差异（P〉0．05）,但在低分化前列腺癌组织中的表达强阳性率明显低于高分化前列腺癌（P〈0．05）。结论PARP-1和PAR存前列腺癌组织的表达明显增加,为前列腺癌的诊断提供了参考,其与前列腺癌进展的相关性有待进一步研究。     

CIP2A在前列腺癌中的表达及临床意义

目的:探讨蛋白磷酸酶2A的癌性抑制因子(CIP2A)蛋白在前列腺癌中的表达及临床意义。方法:应用免疫组织化学方法对前列腺癌(65例)和良性前列腺增生(30例)标本中CIP2A蛋白表达进行检测,将CIP2A染色分数与临床病理参数进行对照研究。结果:CIP2A在前列腺癌组织中的表达较良性增生组织明显增加(P0.01);CIP2A的表达与Gleason评分具有相关性(P0.01);接受根治性前列腺切除术的患者,CIP2A表达与危险分级(P=0.011)相关,但CIP2A表达和PSA浓度之间无明显的相关性。结论:CIP2A蛋白在前列腺癌组织中的表达增加,其表达与肿瘤的低分化和高风险明显相关。     

同源框基因NKX3.1在前列腺癌组织中的表达及意义

目的　探讨同源框基因NKX3.1在前列腺癌中的表达意义。　方法　采用半定量RT PCR检测前列腺癌、良性前列腺、非前列腺组织标本NKX3.1mRNA表达状况并对其扩增产物进行测序。　结果　 76例前列腺组织中 ,NKX3.1表达 75例 ,表达率 98.7%。 96例非前列腺组织标本中 ,除 2例睾丸组织、1例乳腺组织有NKX3.1表达外 ,肾、膀胱、肝、回肠、脂肪、皮肤组织无 1例表达。前列腺癌组织NKX3.1表达量明显增高 ,良性前列腺增生组织表达量明显减弱 (P <0 .0 1) ;晚期前列腺癌组织NKX3.1表达明显高于早期前列腺癌 (P <0 .0 5 ) ;低分化前列腺癌表达高于中高分化前列腺癌 (P <0 .0 5 ) ;激素依赖性前列腺癌表达高于激素非依赖性前列腺癌 (P <0 .0 1)。NKX3.1表达高低与前列腺体积和血清总PSA浓度无关 (P >0 .0 5 )。　结论　NKX3.1基因具有前列腺组织特异性 ,其表达状况与前列腺癌分期、分级相关。NKX3.1表达对于判断前列腺癌病理生物学特性和前列腺癌治疗有重要意义。     

前列腺癌组织中TRIB1基因和蛋白异常表达与患者不良预后的相关性

目的研究Tribbles同源蛋白1(TRIB1)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患者临床特征及预后的关系。方法在公共基因芯片数据库(GEO)中下载前列腺样本中的相关基因芯片数据,分析TRIB1在前列腺样本中mRNA的表达水平。收集临床手术切除或者穿刺活检的前列腺癌和前列腺增生组织,通过免疫组化检测前列腺癌、前列腺增生组织中TRIB1蛋白的表达。分析TRIB1蛋白和基因的表达水平与患者临床特征及预后的关系。结果前列腺癌患者组织中TRIB1蛋白表达显著上调(P0.01),TRIB1蛋白表达上调与前列腺癌Gleason评分(P0.01)、病理分期(P=0.02)相关,基因芯片数据提示TRIB1基因表达上调与前列腺癌Gleason评分(P=0.02)、病理分期(P=0.01)、无生化复发生存率(BCR-free survival)(P=0.047)相关。结论 TRIB1在前列腺癌组织中表达上调,前列腺组织中检测TRIB1可能有助于判断前列腺癌分化程度并评估预后。     

前列腺癌TSP-1的表达与血管新生的关系及意义

目的：探讨良性前列腺增生及前列腺癌中血管生成与血小板反应素-1（TSP-1）表达的相关性。方法：应用免疫组织化学方法检测32例良性前列腺增生和32例前列腺癌组织中TSP-1的表达及微血管密度（MVD）。结果：前列腺癌组织中TSP-1表达显著低于良性前列腺增生（P〈0．05）,MVD则明显升高（P〈0．05）;随着肿瘤分期的进展,浸润转移性癌中TSP-1的表达降低甚至缺失,而MVD却逐渐升高。结论：TSP-1在前列腺癌中呈低表达,与前列腺癌的血管新生相关;作为一种内源性血管新生抑制剂,它具有抑制肿瘤生长及血管新生的作用。     

MUC1 Expression in Prostate Carcinoma: Correlation with Grade and Stage

Mucins have been implicated in the biologic behavior and progression of several types of cancer. The aims of this study were to define the expression pattern of one particular mucin, MUC1, in benign and malignant human prostate tissue and to determine if MUC1 expression correlates with tumor grade and stage. Immunohistochemical staining utilizing an anti-MUC1 monoclonal antibody was performed on 4 fetal prostates, 4 specimens of benign prostatic hyperplasia (BPH), and 34 radical prostatectomy specimens. In human fetal and BPH specimens, there was an apical pattern of MUC1 expression, similar to that reported in other normal and benign tissues. Ninety-four percent of the prostate cancers were MUC1 positive. A high percentage of prostate cancer specimens (62%) demonstrated a diffuse, cytoplasmic staining pattern. There was a statistically significant correlation between diffuse MUC1 staining and Gleason pattern, with a diffuse/total staining percentage of 9% in Gleason 2, 64% in Gleason 3, 80% in Gleason 4, and 100% in Gleason 5. More diffuse staining was also seen in samples from patients with high pathologic stage: 21% in T(2), 75% in T(3), and 67% in N(1) disease. These data indicate that MUC1 expression is prevalent in prostate cancer and that diffuse cytoplasmic staining correlates with advanced Gleason pattern and advanced pathologic stage.     

Expression of a human cell adhesion molecule, MUC18, in prostate cancer cell lines and tissues

BACKGROUND: Over expression of huMUC18, a cell adhesion molecule in the immunoglobulin gene superfamily, causes a non-metastatic human melanoma cell line to become metastatic in a nude mouse system. To determine if MUC18 expression correlates with the malignant progression of prostate cancer, we investigated differential expression of human MUC18 (huMUC18) in normal prostate epithelial cells, prostate cancer cell lines, and prostatic normal and cancer tissues. METHODS: RT-PCR and Western blot analyses were used to analyze the expression of MUC18 mRNA and protein in four human prostate cancer cell lines, cultured primary normal prostate epithelial cells, normal prostate and malignant prostate tissues. Immunohistochemistry was used to determine the expression of MUC18 antigen in prostatic tissues at different stages of malignancy. RESULTS: Human MUC18 mRNA and protein was expressed in three different prostate cancer cell lines (TSU-PR1, DU145, and PC-3), but not in one prostate cancer cell line (LNCaP.FGC). HuMUC18 protein was also expressed at high levels in extracts prepared from tissue sample sections containing high grade prostatic intraepithelial neoplasia (PIN), but weakly expressed in extracts prepared from either cultured primary normal prostatic epithelial cells or the normal prostate gland. Immunohistochemical analysis showed that huMUC18 was expressed at higher levels in the epithelial cells of high-grade PIN and prostatic carcinomas and in cells of a lymph node metastasis compared to that in normal or benign hyperplastic epithelium (BPH). CONCLUSIONS: We therefore conclude that MUC18 is expressed at higher levels in pre-malignant and malignant prostatic epithelium, including metastasis. We suggest that over-expression of MUC18 may be a new marker of human prostate cancer and also implicates its possible role in development and progression of prostate cancer.     

Expression of sialylated MUC1 in prostate cancer: Relationship to clinical stage and prognosis

Aim: MUC1 is distributed among a variety of normal epithelial tissues, and overexpression of MUC1 is detected in several human cancers. This study aimed to elucidate whether sialylated MUC1 expression correlated with: (i) clinical stage of prostate cancer; (ii) pathological grade of prostate cancer; (iii) pretreatment serum level of prostate‐specific antigen (PSA); or (iv) the disease prognosis in patients with prostate cancer who received endocrine therapy. Methods: We collected 57 biopsy specimens from prostate cancer patients treated with only endocrine therapy, and 10 specimens of normal prostates. These specimens were stained immunohistochemically by using a novel monoclonal antibody, MY.1E12, to detect sialylated MUC1. The levels of expression, clinical stages, pathological grades, pretreatment serum level of PSA and the prognoses of the patients were statistically analyzed for correlations. Results: There were statistically significant correlations between the expression of sialylated MUC1 and pathological grades (WHO grade, P < 0.01; Gleason score, P < 0.05). Expression increased according to the progression of the disease (existence of clinical metastasis, P < 0.05; clinical T‐stage, P < 0.01). Patients with high serum levels of PSA had higher expression than those with low levels (P < 0.01). The level of sialylated MUC1 significantly correlated with progression‐free survival (P < 0.01) and cause‐specific survival (P < 0.01) according to univariate analyses. Furthermore, the level significantly correlated with progression‐free survival according to multivariate analysis. Conclusions: These results suggest that sialylated MUC1 plays an important role in the progression of prostate cancer, and that its expression level in the primary lesion is a useful marker for the prognoses of patients undergoing endocrine therapy.     

MUC1, MUC2, MUC4, and MUC5AC expression in salivary gland mucoepidermoid carcinoma: diagnostic and prognostic implications

We determined whether immunostaining for mucins could provide a better characterization of salivary gland mucoepidermoid carcinoma (MEC). We investigated 63 MECs by immunohistochemistry for MUC1, MUC2, MUC4, and MUC5AC. Mucin expressing cell types and labeling patterns were recorded. The results were compared with microscopic grade, tumor-associated lymphoid infiltrate, mucin expression in surrounding salivary glands, clinical features, and outcome. MUC1 and MUC4 labeled the apical membrane of glandular tumor cells and the entire membrane of intermediate, clear, and epidermoid tumor cells. MUC2 and MUC5AC were expressed in the cytoplasm of glandular, mucous, and intermediate tumor cells. In contrast to MUC1, MUC4 expression decreased with tumor grade (P < 0.01). Unlike MUC2, MUC5AC was expressed in more than 50% of high-grade tumors, including 2 cases that were not stained with Alcian blue. MUC1 and MUC5AC were associated with tumor-associated lymphoid infiltrates (P < 0.05), but not with tumor-associated lymphoid follicles. The proportions of tumors expressing mucins were 71% for MUC1, 21% for MUC2, 79% for MUC4, and 68% for MUC5AC. MUC1 and MUC5AC were more frequently expressed in tumors than in surrounding glands (P < 0.0001). MUC1 expression correlated with shorter progression-free survival (P < 0.05). In conclusion, mucin expression in MEC differs from that in salivary glands. Intermediate cells express MUC1 and MUC4 all along their cell surface and MUC2 and MUC5AC in their cytoplasm. Staining for MUC5AC in high-grade tumors can be helpful for distinguishing high-grade MEC from squamous cell carcinoma. While MUC4 is related to tumor differentiation, MUC1 expression indicates a worse prognosis.     

Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score

OBJECTIVE: To investigate the expression and potential clinical usefulness of structure-specific flap endonuclease 1 (FEN-1) in human primary prostate cancer using tissue microarray technology, as FEN-1 was recently identified to be overexpressed in CL1.1, the most aggressive clone generated from the hormone-refractory prostate cancer cell line CL1. MATERIALS AND METHODS: Immunohistochemistry was performed on tissue microarrays constructed from paraffin-embedded specimens of primary prostate cancer from 246 patients who had had a radical prostatectomy. Prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH) and normal prostate epithelium were represented on the array. FEN-1 nuclear expression was scored based on the percentage of target cells staining positively, and correlated with Gleason score, preoperative prostate-specific antigen (PSA) level and pathological stage. The time to PSA recurrence was also analysed. RESULTS: The mean expression of FEN-1 was significantly higher in cancer (36.7%) than in normal (13.2%), BPH (4.5%) and PIN (15.4%) specimens (P < 0.001). FEN-1 expression was significantly correlated with Gleason score (ó = 0.23, P = 0.002). A higher preoperative serum PSA level (P = 0.015), Gleason score > or = 7 (P < 0.001), seminal vesicle invasion (P < 0.001) and capsular involvement (P = 0.004) were associated with PSA recurrence, whereas FEN-1 expression was not. In a multivariate analysis, only Gleason score > or = 7 (P < 0.001), seminal vesicle invasion (P = 0.005) and capsular involvement (P = 0.009) were retained as independent predictors for PSA recurrence. CONCLUSIONS: FEN-1 is overexpressed in prostate cancer compared with matched normal prostate, and its expression increases with tumour dedifferentiation, as shown by increasing Gleason score. These results suggest that FEN-1 might be a potential marker for selecting patients at high risk, and a potential target for prostate cancer diagnosis and therapy.     

肿瘤标记物P504s在前列腺癌中的表达及应用价值

目的探讨肿瘤标记物P504s在不同前列腺组织中的表达情况,及在诊断前列腺癌中的应用价值。方法采用免疫组化二步法,观察P504s和基底细胞标记物p63在不同前列腺病变组织中的表达情况。结果①P504s表达在前列腺癌根治标本、高等级上皮内瘤标本、前列腺增生标本中的阳性率分别为91.4%（32/35）、87.0%（20/23）和0（0/30）,良恶性组织的差别有显著性,在前列腺癌穿刺标本中阳性率85.7%（72/84）。p63染色在全部前列腺癌中呈阴性,在高等级上皮内瘤中为不连续或连续的阳性染色,在前列腺增生中为连续的阳性染色。②P504s表达与前列腺癌的分化程度、激素治疗、转移有关。结论P504s是一个特异的前列腺癌标记物,结合p63在鉴别诊断前列腺癌中有重要的临床应用价值。     

Expression of insulin-like growth factor-1 receptor in local and metastatic prostate cancer

PURPOSE: The insulin-like growth factor (IGF)-1 receptor is currently being targeted in clinical trials in prostate cancer. Despite this targeting, there are conflicting data on the presence of this receptor in human tumor samples, largely because of differences in technique. MATERIALS AND METHODS: Immunohistochemistry was used to determine the presence of IGF-1 receptor in frozen normal prostate and prostate cancer specimens. Clinical and pathologic parameters were correlated with IGF-1 receptor intensity and frequency of staining. Only 2-3+ staining on a scale of 0-3 was considered positive in this evaluation. RESULTS: IGF-1 receptor was expressed in normal prostate epithelium in 6 of 6 patients without cancer and in morphologically normal epithelium adjacent to tumor cells in 21 of 22 patients with cancer studied. IGF-1 receptor was present in the prostate tumor epithelium of 28 of 28 primary tumors, 3 of 5 locally recurrent androgen-independent tumors, and in 4 of 5 metastatic lymph nodes. Stromal staining patterns were positive in 2 of 28 specimens near benign epithelium compared to 19 of 30 specimens of stroma surrounding tumor epithelium (P < 0.0001, Fisher exact test). Stroma adjacent to Gleason grade >or=7 tumors showed higher intensity staining than that adjacent to lower grade tumors (P < 0.001). Expression of the closely related insulin receptor did not show expression in either normal or cancer epithelium, or in adjacent stroma. CONCLUSIONS: This study using frozen tissue shows widespread IGF-1 receptor expression in normal prostate, prostate cancers, and metastases. These data support investigations into IGF-1 receptor as a therapeutic target in prostate cancer.     

Cytoplasmic induction and over-expression of cyclooxygenase-2 in human prostate cancer: implications for prevention and treatment

OBJECTIVE: To assess the level and morphological distribution of cyclooxygenase (COX)-1 and -2 in human prostates and to determine any association with the Gleason grade of prostate cancer. Materials and methods The study comprised 30 samples from patients with benign prostatic hyperplasia (BPH) and 82 with prostate cancer. Immunohistochemistry was used to assess the expression of COX-1 and -2, and 13 samples were also assessed using immunoblotting (six BPH and seven cancers). RESULTS: For both BPH and prostate cancer, COX-1 expression was primarily in the fibromuscular stroma, with variable weak cytoplasmic expression in glandular/neoplastic epithelial cells. In contrast, COX-2 expression differed markedly between BPH and cancer. In BPH there was membranous expression of COX-2 in luminal glandular cells and no stromal expression. In cancer the stromal expression of COX-2 was unaltered, but expression by tumour cells was significantly greater (P = 0.008), with a change in the staining pattern from membranous to cytoplasmic (P < 0.001). COX-2 expression was significantly higher in poorly differentiated than in well differentiated tumours (P < 0.001). These results were supported by immunoblotting, which showed similar levels of COX-1 in both BPH and cancer, but four times greater expression of COX-2 in cancer than in BPH. CONCLUSION: This is the first study to assess the co-expression of COX-1 and COX-2 proteins in benign and malignant human prostates, and showed the induction and significantly greater expression of COX-2 in cancer, which was also associated with tumour grade. The regular use of nonsteroidal anti-inflammatory drugs is associated with a reduced incidence of cancers. The present results provide the basis for a potential role for COX-2 inhibitors in the prevention and treatment of prostate cancer.