Immunoreactivity of p27<Superscript>(Kip1)</Superscript>, cyclin D3, and Ki67 in conventional renal cell carcinoma

The goal of the study was to evaluate expression of the cell-cycle regulatory proteins (p27^(Kip1) and cyclin D3) and proliferation marker Ki67 in normal human kidneys and renal cell carcinoma (RCC) tissues. Intensity of the markers’ expression was prospectively studied and compared between normal and RCC tissue samples. Association was analyzed with cancer clinical parameters. p27^(Kip1) was significantly upregulated in normal compared with in RCC samples. Immunoreactivity of the protein negatively correlated with tumor size and was associated with pathological stage and grade. Patients with symptomatic disease had significantly less marker expression than those with incidentally discovered tumors. Intensity of Ki67 staining positively correlated with primary tumor size and associated with disease stage and grade. Cyclin D3 immunoreactivity positively correlated with tumor size. Loss of p27^(Kip1) expression, pathological stage, grade, and tumor size were risk factors for disease recurrence (P = 0.0072, 0.0011, and 0.0467, and P < 0.0001, respectively) and patient death (P = 0.0021, 0.0106, 0.0151, and 0.0021, respectively). With Cox multivariate analysis loss of p27^(Kip1) expression (hazard ratio 9.3, P = 0.002) and tumor size (hazard ratio 5.9, P = 0.015) were the predictors of cancer-specific survival. In conclusion, intensity of the markers’ expression in RCC is associated with tumour clinical parameters (size, stage, grade, and disease presentation type). Loss of p27^(Kip1) expression is a risk factor for the disease recurrence and cancer-related patient death.     

Loss of p27<Superscript>(Kip1) </Superscript>CDKI is a predictor of poor recurrence-free and cancer-specific survival in patients with renal cancer

The importance of cyclin-dependent kinase inhibitors (CDKI) in benign and malignant urological diseases is a subject of intense ongoing investigation. The goal of the current study was to analyze the expression of p27^(Kip1) CDKI in benign and malignant renal cells and assess their possible association with different clinical parameters. Expression of p27^(Kip1) was evaluated and compared in 24 normal human kidneys and in 52 renal cell carcinoma (RCC) tissue samples. Intensity of the expression was compared between the groups and association was analyzed with cancer clinical parameters. The expression of the marker was significantly higher in normal than in RCC samples (P = 0.0045). Intensity of p27^(Kip1) expression in RCC was negatively correlated with tumor size (Rho = −0.438, P = 0.0051) and associated with pathological stage and grade (P = 0.0488 and < 0.0001, respectively). The patients with symptomatic disease had significantly less marker expression than incidentally discovered tumors (P = 0.0301). Loss of p27^(Kip1) expression, pathological stage, grade and tumor size were the risk-factors for disease recurrence (P = 0.0072, 0.0011, 0.0467 and < 0.0001, respectively) and patient survival (P = 0.0021, 0.0106, 0.0151 and 0.0021, respectively). With Cox multivariate analysis loss of p27^(Kip1) expression (hazard ratio 9.3, P = 0.002) and tumor size (hazard ratio 5.9, P = 0.015) were the predictors of cancer-specific survival. Expression of p27^(Kip1) is significantly decreased in RCC as compared with normal kidney tissue. Intensity of the expression is associated with clinical parameters: tumor size, stage, grade and disease presentation. Loss of p27^(Kip1) expression is a risk-factor for disease recurrence and the strongest predictor of cancer-specific survival.     

Insulin-like growth factor (IgF)-I,IgF binding protein-3, and prostate cancer: correlation with gleason score

Introduction

Non-androgenic growth factors are involved in the growth regulation of prostate cancer (PCa).

Objective

This is the first Brazilian study to correlate, in a population of patients operated for PCa, PSA, total testosterone, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) with Gleason score and to compare with a control group with benign prostate hyperplasia (BPH).

Materials and Methods

This retrospective single-center study included 49 men with previously diagnosed PCa and 45 with previously diagnosed BPH. PSA, testosterone, IGF-I, IGFBP-3 were determined in both groups.

Results

PSA and IGFBP-3 levels were significantly higher in the PCa group as compared to the BPH group (p<0.001 and p=0.004, respectively). There was a significant difference when we compared the PSA before surgery (p<0.001) and at the inclusion in the study (p<0.001) and IGFBP3 (0.016) among patients with Gleason <7, ≥7 and BPH. In the PCa group, PSA, testosterone, IGF-I and IGFBP-3 levels were comparable between Gleason <7 and ≥7.

Conclusions

Our data suggest that in localized PCa, the quantification of PSA and, not of IGF-1, may provide independent significant information in the aggressiveness. IGFBP-3 could be a biochemical marker of disease control in PCa patients.     

Inverse relationship between Skp2 ubiquitin ligase and the cyclin dependent kinase inhibitor p27Kip1 in prostate cancer

PURPOSE: Prostate carcinomas show a low level of the cell cycle inhibitor p27, which correlates with tumor aggressiveness. In tumors p27 is of the WT species and its deregulation is due to aberrant ubiquitin mediated degradation. The p27 is degraded following phosphorylation and subsequent recognition by SCFSkp2 ubiquitin ligase. We examined the relationship between p27 and its specific ligase Skp2 in normal and malignant prostate tissues. A possible correlation among the levels of these proteins, tumor grading and clinical state was also investigated. MATERIALS AND METHODS: Using immunohistochemistry immunofluorescence microscopy and Western blot analysis 51 samples from needle biopsies, transurethral resection and radical prostatectomy were analyzed for p27 and Skp2 expression. Correlation with tumor grading (Gleason) was performed. In 22 proven metastatic or organ confined cases correlation was also done with the Ki67 proliferative marker. RESULTS: Skp2 expression demonstrated a significant and direct correlation with malignancy (p <0.0001). Furthermore, a significant correlation was found between Skp2 level and tumor aggressiveness graded by Gleason score (p <0.0002) and prostate specific antigen. Patients with metastases had significantly higher Skp2 and Ki67 expression than those with organ confined disease (p <0.0001). In addition, Skp2 levels significantly correlated with Ki67 (r = 0.73, p <0.0001). An inverse correlation was found between p27 and Skp2 ligase. CONCLUSIONS: Skp2 expression in prostate biopsies may be used as an additional marker for tumor aggressiveness. The results also suggest a role for Skp2 in the pathogenesis of prostate malignancy.     

Expression of the ubiquitin ligase subunit cyclin kinase subunit 1 and its relationship to S-phase kinase protein 2 and p27Kip1 in prostate cancer

PURPOSE: Loss of the cell cycle inhibitory protein p27Kip1 in cancer is associated with tumor aggressiveness and poor prognosis in the prostate. The decrease in p27(Kip1) results from increased proteasome dependent degradation, which is mediated by its specific ubiquitin ligase subunits S-phase kinase protein 2 and cyclin dependent kinase subunit 1. S-phase kinase protein 2 was found to be over expressed in aggressive prostate cancers but to our knowledge the role of cyclin dependent kinase subunit 1 in these cancers is unknown. MATERIALS AND METHODS: The expression of cyclin dependent kinase subunit 1, S-phase kinase protein 2 and p27Kip1 was examined by immunohistochemistry in tissue sections from 45 patients with prostate cancer. The expression of cyclin dependent kinase subunit 1 was compared to that of S-phase kinase protein 2 and p27Kip1, and patient clinical and histological characteristics. RESULTS: Cyclin dependent kinase subunit 1 expression was strongly associated with S-phase kinase protein 2 expression (r = 0.666, p = 0.001) and inversely with p27Kip1 expression (r = -0.737, p < 0.001). Cyclin dependent kinase subunit 1 over expression was associated with loss of tumor differentiation (r = 0.631, p = 0.001), high serum prostate specific antigen (r = 0.627, p < 0.001) and metastatic disease (p < 0.001). CONCLUSIONS: These results suggest that cyclin dependent kinase subunit 1 is involved in p27Kip1 down-regulation and it may have an important causative role in the development of aggressive tumor behavior in prostate cancer.     

XAGE-1 b基因在良性前列腺增生症与前列腺癌中的表达及其意义

目的 观察XAGE-1b基因在良性前列腺增生症和前列腺癌中的表达,探讨其数值对良性前列腺增生症和前列腺癌各项指标的临床意义.方法 运用实时荧光定量聚合酶链反应(PCR)方法检测38例前列腺癌病理组织以及40例良性前列腺增生症组织XAGE-1b的基因表达水平.结果 XAGE-1b在前列腺癌组织中表达值为8.299 50±0.97116,在良性前列腺增生症组织中表达值为3.007 80±0.91600,差异有统计学意义(P＜0.05).XAGE-1b表达值随着Gleason评分、临床分期和肿瘤恶性程度升高而表达增强(P＜0.05).结论 XAGE-1b基因高表达值有助于前列腺癌的诊断和指导前列腺癌的恶性程度分期.

Abstract：

Objective To study the XAGE-1 b mRNA expression in prostate cancer (PCa) tissues and benign prostate hyperplasia (BPH) tissues,and explore the diagnostic values of XAGE-1 b mRNA expression level in PCa and BPH.Methods A sensitive,real-time quantitative polymerase chain reaction (PCR) assay was developed to compare the expression difference of XAGE-1b mRNA in PCa and BPH tissues,by testing 38 samples of PCa and 40 samples of BPH.Results The expression level of XAGE-1 b in PCa tissue was 8.299 50 ± 0.971 16,and 3.007 80 ± 0.916 00 in BPH tissue ( P＜0.05 ).The XAGE-1 b expression levels were increased with the increase of the Gleason score,clinical stage and malignant grade (P＜0.05).Conclusion The high expression of of XAGE-1 b mRNA can afford a reliable and helpful information for diagnosis of PCa and BPH,and PCa malignant grade.     

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.     

Total thiol can contribute to differentiating prostate cancer from BPH: Prostate Thiol Index as a new player

To assess the distinctiveness of serum native thiol (NT), total thiol (TT) and disulfide (SS) levels in PCa patients, we created a new parameter, prostate thiol index (PTI) [tPSA (TTxPVxAge) ^−1/2]. We determined the performance of the PTI on PCa diagnosis. A total of 107 male patients (PCa:65; BPH:42) who were separated according to their Gleason scores, ISUP grades and EAU risk groups and 20 healthy subjects were included. The performances of the tests were determined. The PCa and BPH groups had lower NT and TT levels and higher SS levels than the control group. PCa patients had higher PTI, tPSA, fPSA, PSAD levels, lower fPSA%, PV and PSA-AV levels than BPH patients. TT, PTI, tPSA, fPSA, fPSA%, PSA-AV, PSAD and PV had significant diagnostic performances. PTI had the highest AUC value and accuracy, PSA-AV had the highest specificity, and fPSA had the lowest sensitivity. The performance of the PTI was the best in distinguishing PCa from BPH. PTI, tPSA and PSAD positively and PSA-AV negatively correlated with ISUP grades and EAU groups. TT can contribute to the discrimination of PCa from BPH and PTI may decrease unnecessary biopsies in clinical practice.     

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.     

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。     

Expression of cyclin A and D proteins in prostate cancer and their relation to clinopathological variables and patient survival

BACKGROUND: Cell proliferation and its regulation are important determinants of the prognosis of prostate cancer patients. Cyclins are important regulators of cell proliferation in human cancer, but their prognostic value has not been previously analyzed in prostate cancer. METHODS: The immunohistochemical expression and prognostic value of cyclins A and D were studied in prostate cancer in a cohort of 213 patients followed-up for a mean of 12 years. RESULTS: The expression of cyclin A was both cytoplasmic and nuclear, whereas the expression of cyclin D was nuclear. The mean (SD) fraction of cyclin A- and cyclin D-positive cells was 2.1 (7.9)% and 16.3 (23.4)%, respectively. The expression of cyclin A was related to TM-category, histological differentiation, perineural invasion, S-phase fraction, and expression of Ki67 and bcl-2 (for all, P<0.05). The expression of cyclin D was related to TM-classification, histological differentiation, perineural invasion, DNA ploidy, S-phase fraction, expression of Ki67, and mitotic index (for all, P< or =0.01). In survival analysis, expression of cyclin A predicted cancer-related survival in the entire cohort (P<0.001). Expression of cyclin D predicted cancer-related survival in the entire cohort (P<0.0001), in MO (P = 0.0007), and in T1-2NxM0 tumors (P = 0.0003). In Cox multivariate analysis, T-category, M-category, patient age, and the fraction of cyclin A-positive cells were independent predictors of survival in the entire series. In local tumors, T-category, Gleason score, DNA ploidy, or S-phase fraction were independent prognostic factors, and cyclins had no independent prognostic value. CONCLUSIONS: The results show that the expression of cyclins A and D is related to several malignant cellular features in prostate cancer, but they have no independent prognostic value.     

Absence of the Cell Cycle Inhibitor p27Kip1 Protein Predicts Poor Outcome in Patients With Stage I-III Colorectal Cancer

Background: The p27^Kip1 protein regulates the G1 to S phase transition of cell cycle by binding to and inhibiting the cyclin E/Cdk2 complex. This study explores the prognostic significance of the absence of the p27^Kip1 protein in patients with colorectal cancer (CRC).Methods: Formalin-fixed tumor sections from 124 patients who underwent curative resection for stage I-III CRC were analyzed by immunohistochemistry using MoAb anti-p27^Kip1.Results: Detectable levels of p27^Kip1 protein were found in 86% of tumors. Median follow-up was 55 months. Actuarial 5-year disease-free survival (DFS) and overall survival (OS) were 76% and 85%, respectively, in patients with tumors with p27^Kip1 protein expression and 34% and 40%, respectively, in those whose tumors lacked p27^Kip1 protein expression (P < .001). At multivariate analysis, tumor stage (III vs. I-II) and p27^Kip1 protein status (absence vs. presence) were found to be independent prognostic factors for DFS and OS.Conclusions: Lack of p27^Kip1 protein expression in CRC is a negative prognostic marker and may therefore be useful in selecting early-stage patients more likely to benefit from adjuvant treatment.Presented at the 51st Annual Cancer Symposium of The Society of Surgical Oncology, San Diego, California, March 26–29, 1998.     

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。     

人前列腺癌组织和良性前列腺增生组织中p27kip1和CDKs的表达

目的　观察前列腺癌 (PCa)细胞中CDKs和p2 7kip1的蛋白表达。方法　采用蛋白印渍、电转移方法 (Westernblot)检测 15例人前列腺癌组织和 15例前列腺增生组织标本中CDKs和p2 7kip1的表达。结果　所有标本的非癌组织中均有较强的 p2 7kip1和CDK2 ,CDK4及CDK6蛋白表达。 15例人前列腺癌组织中与周边非癌组织比较有 11例 p2 7kip1蛋白表达明显降低 ,其中 5例术后发生转移的标本中有 4例 p2 7kip1蛋白表达降低。 15例前列腺增生组织标本增生组织和周边正常组织中 p2 7kip1蛋白表达强度相同。而所有标本中未见有CDKs (CDK2 ,CDK4,CDK6)蛋白表达在癌与周边非癌组织、增生组织与正常组织中的强度差别。结论　p2 7kip1蛋白的表达异常降低特异性见于人前列腺癌细胞中 ,和前列腺癌的发生有关。     

PIM-1在前列腺癌组织中的表达及其与PSA的关系

目的:探讨PIM-1蛋白在前列腺癌组织中的表达及其与PSA复发之间的关系。方法:利用免疫组化SP检测68例前列腺癌和37例良性前列腺增生(BPH)组织中PIM-1蛋白的表达。结果:在前列腺癌组织中PIM-1蛋白表达的阳性率为67.65%(46/68);BPH组织中40.54%(15/37),两组表达的差异有显著意义(P<0.05)。PIM-1蛋白表达的阳性率在前列腺癌Gleason分级中6分33.33%(7/21),7分75%(21/28),8～10分94.74%(18/19),组间比较差异有显著性(P<0.05)。临床分期中在Ⅰ、Ⅱ、Ⅲ、Ⅳ期PIM-1蛋白表达率分别为47.62%、53.85%、73.33%、94.74%,36个月随访PSA复发状况采用Kaplan-Meier方法分析,PIM-1蛋白表达与有无复发分别是78.26%(36/46)和45.45%(10/22),差异有显著性(P<0.05)。结论:前列腺癌中PIM-1蛋白表达与前列腺癌的Gleason分级、临床分期以及PSA复发有密切关系,提示PIM-1基因在前列腺癌演化和进展中有重要作用,可能是前列腺癌的预后指标。     

Mcl-1和Caspase-3在前列腺癌患者中的表达和意义及相关性分析

目的 观察Mcl-1和Caspase-3在前列腺癌（PCa）、良性前列腺增生（BPH）组织中的表达情况,探讨两者相关性及意义。方法 采用免疫组化法检测并比较分析30例BPH和35例不同病理分级的PCa组织切片Mcl-1、Caspase-3蛋白的表达。结果 PCa组Mcl-1阳性表达率为82.86%（29/35）,显著高于BPH组13.33%（4/30,P<0.05）;PCa组Caspase-3阳性表达率为25.71%（9/35）,显著低于BPH组73.33%（22/30）（P<0.05）。Mcl-1、Caspase-3蛋白的表达与PCa患者术前PSA值、有无远处转移、Gleason评分、临床分期等临床资料无关(P>0.05)。在PCa组织中Mcl-1的表达与Caspase-3的表达呈负相关（r_s=-0.748,P<0.05）。结论Mcl-1、Caspase-3在PCa的发生、发展中可能相互影响。     

miR-18a在前列腺癌患者血清中的表达及其临床意义

目的探讨前列腺癌患者microRNA-18a(miR-18a)在血清中的表达及其诊断价值。方法采用实时荧光定量PCR(qRT-PCR)检测60例前列腺癌患者(PCa)、30例良性前列腺增生患者(BPH)和20例健康对照者(HC)血清miR-18a的表达水平。分析miR-18a表达水平与前列腺癌Gleason分级、TNM分期及PSA的关系。通过分析受试者工作特征(ROC)曲线判断miR-18a表达水平在前列腺癌诊断中的灵敏度和特异度。结果PCa患者血清miR-18a的表达水平分别明显高于BPH组和HC组(P<0.01);miR-18a与Gleason评分、肿瘤分期有关(P<0.01);miR-18a与PSA之间呈正相关(r=0.701,P=0.000);miR-18a的ROC曲线下面积(AUC)为0.928(95%CI:0.880~0.976,P=0.000),敏感度为84.3%,特异度为75.8%。结论miR-18a在PCa患者血清中表达水平明显增高,对于PCa的诊断有潜在的临床参考价值。     

6种microRNAs在前列腺癌组织中的表达

目的:研究表明miRNAs在人类恶性肿瘤的发生发展过程中起着重要作用,本研究检测6种miRNAs:miR-98、let-7d、let-7g、miR-96、miR-182及miR-183在前列腺癌组织中的表达情况及其临床意义。方法:采用原位分子杂交方法,结合组织芯片技术分别检测38例BPH和52例前列腺癌中6种miRNAs的表达情况。并对前列腺癌组织中6种miRNA与Gleason评分,临床分期及6种miRNA间进行相关分析。结果:6种miRNAs中,与BPH组织相比,在前列腺癌组织中表达降低的为miR-98、let-7d、let-7g;而表达升高的为miR-96、miR-182及miR-183,差异均有统计学意义(P<0.05)。6种miRNAs的表达与前列腺癌的Gleason评分均相关(P<0.05),但与患者的年龄及血清PSA水平均无明显相关性(P>0.05)。其中miR-96和miR-182的表达与前列腺癌的临床分期均有相关性(P<0.05),miR-98和miR-96的表达均与肿瘤累及前列腺的叶数存在相关性(P<0.05)。另外,前列腺癌组织中,miR-96、miR-182及miR-183的表达彼此之间呈正相关(P<0.01,r分别为0.41,0.44),let-7d与let-7g的表达之间呈正相关(P<0.01,r=0.46),miR-98与let-7d及let-7g的表达之间呈正相关(P<0.05,r分别为0.31,0.34)。结论:miR-98、let-7d、let-7g、miR-96、miR-182及miR-183构成的miRNA表达谱在一定程度上反映了前列腺癌的生物学行为,可能作为前列腺癌早期诊断和预后评估的重要生物标记物。     

Cyclin E and Ki67 (MIB1) as markers of proliferative activity in human prostate cancers: an immunohistochemical study

Recent evidence has implicated cyclins in the evolution and progression of various malignancies. We immunohistochemically evaluated the expression of cyclin E, a G1 cyclin, along with Ki67-assessed proliferative activity in prostatic carcinoma. Formalin-fixed, paraffin embedded tissue sections from eighty-four previously untreated prostate carcinomas were distributed according to tumor grade and examined for the expression of cyclin E. Results were compared with Ki67 expression as well as tumor grade. Cyclin E was detected in 22 of 84 cases (26.2%) and its expression varied substantially (mean index varied from 4,7–9,0). Ki67 staining was present in 35.7% of cases. Although no correlation with tumor grade was found for either cyclin E or Ki67, a statistically significant correlation was present between the expression of the two biomarkers (Fisher's test, p<0.0001). We examined the proliferative activity of prostatic carcinomas of different tumor grades with markers for Ki67 and cyclin E. Our findings indicate that reactivities with these markers are strongly correlated with each other but their expression seems independent of tumor grade. Further studies on the clinical implications of the combined variable of cyclin E and Ki67 expression might disclose a useful prognostic indicator of survival or tumor relapse in patients with prostate carcinoma.