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1.
EMMPRIN and fascin are important factors in tumor invasion and progression. We tested the hypothesis that expression of EMMPRIN and fascin correlate with clinicopathological parameters of renal cell carcinoma (RCC). Immunohistochemical analysis of EMMPRIN and fascin were performed in tissue microarrays of 100 surgical specimens, including 35 clear-cell RCC (CRCC), 21 clear-cell RCC with granular differentiation (GRCC), 12 chromophobe RCC (ChRCC), 8 papillary RCC (PRCC), 9 carcinoma of the collecting duct of Bellini (CDC), 10 clear-cell RCC with sarcomatoid differentiation (SRCC), and 6 metastatic RCC. Average immunoscores of EMMPRIN were 100.8 in CRCC, 195.2 in GRCC, 298.4 in ChRCC, 219.2 in PRCC, 186.1 in CDC, 226.9 in SRCC, and 151.7 in metastatic RCC. Among all included cases, average EMMPRIN immunoscores were 84.6 in grade I, 130.4 in grade II, 184.3 in grade III, and 223.5 in grade IV. Additionally, average immunostaining scores of fascin were 53.6 in CRCC, 289.3 in GRCC, 193.3 in ChRCC, 151.8 in PRCC, 181.3 in CDC, 275.4 in SRCC, and 131.7 in metastatic RCC. Average fascin immunoscores were 59.3 in grade I, 91.6 in grade II, 130.2 in grade III, and 194.7 in grade IV. Higher EMMPRIN and fascin immunoscores also correlated significantly with TNM stages and survival rates in RCC. Significant correlation was found between EMMPRIN and fascin expression. In conclusion, higher expression of EMMPRIN and fascin correlate significantly with histological grades, clinical stages, and survival rates of RCC  相似文献   

2.
PURPOSE: Caveolin-1 is a major structural component of caveolae, which are plasma membrane microdomains implicated in the regulation of intracellular signaling pathways. Previous studies of the expression and function of caveolin-1 in cancer have shown controversial results, indicating that the physiological role of caveolin-1 varies according to cancer type. We evaluated caveolin-1 expression in renal cell carcinoma and investigated its association with pathological features and clinical outcome. MATERIALS AND METHODS: Caveolin-1 expression was evaluated by immunohistochemistry using rabbit polyclonal antibody against caveolin-1 in 60 paraffin embedded primary renal cell carcinoma specimens and 6 metastatic renal cell carcinoma specimens. When more than 50% of all cancer cell cytoplasm stained, the tumor was considered caveolin-1 positive. Associations between caveolin-1 expression, and pathological features and clinical outcomes were analyzed. RESULTS: Of 60 primary tumors 16 (26.7%) and 5 of 6 metastatic tumors (83.3%) were immunoreactive in more than 50% of cancer cells and considered caveolin-1 positive. Although no significant associations between caveolin-1 expression, pathological stage (T stage) and distant metastasis at initial presentation were observed, significant associations between positive caveolin-1 expression and high grade tumor (p = 0.0009) and regional lymph node metastasis at initial presentation (p = 0.0049) and venous invasion (p = 0.0195) were observed. There was no difference in cancer specific survival between caveolin-1 positive and negative groups. However, in 43 patients without metastasis to regional lymph nodes or a distant site at initial presentation (N0M0) the caveolin-1 positive group had significantly shorter progression-free survival than the caveolin-1 negative group (p = 0.0332). CONCLUSIONS: Caveolin-1 over expression could be a common finding in aggressive forms of renal cell carcinoma. Caveolin-1 might have an important role in the invasion and metastatic progression of renal cell carcinoma.  相似文献   

3.
BACKGROUND: Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. MMP-2 and MMP-9 have been reported to be closely associated with tumor invasion and metastasis in various human carcinomas. METHODS: Tissue samples were obtained from 57 patients with renal cell carcinoma (RCC) who underwent radical nephrectomy in our hospital. We examined the expression of MMPs by gelatin zymography and assessed correlations with clinico-pathological parameters and clinical outcomes. RESULTS: We detected bands corresponding to MMP-9, proMMP-2 and active MMP-2. The expression of active MMP-2 and MMP-2 activation ratio (active MMP-2/[proMMP-2 and active MMP-2]) were higher in T3 tumors than in T1 and T2 tumors. There were no significant differences in the expression of proMMP-2, active MMP-2 or MMP-9 for any of the clinico-pathological parameters. Patients with high MMP-2 activation ratio or high MMP-9 had significantly worse cause-specific survival. Interestingly, among patients with stage III RCC, those with high MMP-2 activation ratio or high active MMP-2 had significantly worse cause-specific survival. Univariate analysis showed that histological grade (P = 0.0001), histologic type (P = 0.0005), MMP-2 activation ratio (P = 0.0159), stage (P = 0.0001), MMP-9 (P = 0.0316), and T (primary tumor) category of TNM (primary tumor, lymph node, metastasis) classification (P = 0.0021) were significant predictors of clinical outcome. Multivariate analysis showed that only histological grade (P = 0.002) and stage (P = 0.0099) were independently significant predictors of clinical outcome. CONCLUSION: Activation of MMP-2 appears to play important roles in initiating metastasis, as shown by results obtained with stage III RCC patients. However, further study is needed to confirm this.  相似文献   

4.
PURPOSE: Localized renal cell carcinoma is usually curable by nephrectomy. However, a large fraction of patients already present with metastatic disease, which results in a poor outcome. Currently no clinically relevant screening assay is available to detect early stage renal cell carcinoma. We investigated whether urinary extracellular matrix (ECM) proteins and/or matrix metalloproteinase (MMP) activity may be valuable as a noninvasive indicator of early stage renal cell carcinoma. MATERIALS AND METHODS: Urine specimens from preoperative patients with renal cell carcinoma and healthy controls were collected. The urinary excretion of the ECM proteins collagen IV, laminin and fibronectin was investigated by immunoblotting. MMP activity was assessed by gelatin zymography and by a fluorescence based microtiter plate activity assay. RESULTS: The full-length forms of all 3 ECM proteins investigated were significantly decreased or absent in renal cell carcinoma urine. Based on criteria established in this study this finding would lead to the correct detection of 95% of patients with renal cell carcinoma (21 of 22) with a false-positive rate of 4.5% (1 of 22 controls). All 11 nonmetastatic cases of the lowest clinical stage (T1N0M0) were correctly identified. The absence of urinary ECM proteins was due to significantly increased urinary MMP activity. CONCLUSIONS: Analysis of decreased urinary ECM proteins and analysis of increased MMP activity may have value for the development of a sensitive, high throughput molecular screening assay to detect early stage renal cell carcinoma.  相似文献   

5.
目的 探讨长链非编码RNAMIAT在肾透明细胞癌中的表达情况及与患者临床指标的相关性,分析其作为肾透明细胞癌分子标记物的可能性。方法 通过荧光定量PCR方法 检测MIAT在40例肾透明细胞癌组织和40例癌旁正常组织中的表达情况,同时结合TCGA数据库分析MIAT表达水平与肾透明细胞癌患者临床指标和预后的关系。结果 MIAT在肾透明细胞癌组织中的表达明显高于癌旁正常组织,在肾癌细胞系中的表达明显高于正常肾小管上皮细胞,差异均具有统计学意义(P<0.05)。TCGA数据库资料分析表明,MIAT表达水平与肾癌患者T分期(P<0.001)、M分期呈正相关(P<0.05)。Kaplan-Meier生存分析表明,高表达MIAT的肾癌患者总体生存时间明显低于低表达MIAT的肾癌患者(Log-rankP<0.05)。结论 MIAT在肾透明细胞癌组织和肾癌细胞系中高表达,有可能成为肾透明细胞癌的分子标记物。  相似文献   

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BACKGROUND: Two different subtypes of papillary renal cell carcinoma (PRCC) have so far been identified, type-1 with small cells and pale cytoplasm and type-2 with large cells and eosinophilic cytoplasm. It has generally been accepted that type-1 tumors have favorable features in comparison with type-2 tumors, suggesting that these subtypes could be different clinicopathological entities, and, as a result, that the subtypes need to be characterized. Forty cases of PRCCs were reviewed, with special attention to the distinct clinicopathological difference and the response to cytokine therapy. METHODS: Thirty-five cases of PRCC diagnosed between January 1997 and August 2007 were reviewed. PRCCs were classified according to the criteria of Delahunt and Eble. RESULTS: Of these 40 patients, 20 and 20 were diagnosed to be type-1 and type-2 PRCCs, respectively. No lymphatic or vascular invasion or distant metastasis were observed in patients with type-1 PRCC. The nuclear grade in all type-1 PRCCs was low grade. The nuclear grade (P 相似文献   

8.
PURPOSE: We determined the impact of clinical and pathological factors in the outcome of patients with renal cell carcinoma treated surgically. MATERIALS AND METHODS: We retrospectively reviewed the records of 230 consecutive patients after radical or partial nephrectomy. We analyzed clinical (incidental or symptomatic disease) and pathological (tumor size, histological type, Fuhrman nuclear grade, microvascular invasion and lymph node involvement) parameters. Disease-free and cancer specific survival curves were individualized for each parameter and on multivariate analysis. RESULTS: Median postoperative followup was 34.3 months, median time to recurrence was 22 months and mean overall survival was 130 months. A total of 40 patients (17.3%) presented with local and/or metastatic recurrence and 32 (13.9%) died of the disease. Five-year disease-free and cancer specific survival rates on univariate analysis were 56.7% and 64% for symptomatic tumors, 76.6% and 68% for clear cell carcinoma, 26.9% and 39% for sarcomatoid tumors, 34.7% and 47.5% for high grade tumors, 26.7% and 39.7% for microvascular invasion, 37.5% and 49.1% for tumors larger than 7 cm, and 11% and 32% for lymph node involvement, respectively. On univariate analysis patients with lymph node involvement and microvascular invasion had a poor prognosis. Multivariate analysis showed that the single independent prognostic factor was microvascular invasion. CONCLUSIONS: This study points out different clinical and pathological prognostic factors of survival in patients treated for renal cell carcinoma. Microvascular invasion was the only independent prognostic factor on multivariate analysis.  相似文献   

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目的探讨肾透明细胞癌淋巴管新生与临床病理因素的关系。方法通过免疫组织化学染色方法利用D2-40来标记60例肾透明细胞癌患者标本中的淋巴管,利用光学显微镜测定癌周淋巴管密度(PLVD)并观察癌内淋巴管(ILVs)是否出现,评价PLVD及ILVs与临床病理因素的关系。结果平均PLVD为16.89,按平均值分为两组进行相关性分析表明PLVD与远处转移(P=0.073)、淋巴结转移(P=0.758)、Fuhrman细胞核分级(P=0.866)和肿瘤T分期(P=0.653)无相关性,结果无统计学意义。ILVs的出现与远处转移(P=0.001)、淋巴结转移(P=0.017)及Fuhrman细胞核分级(P=0.002)有相关性,与肿瘤T分期(P=0.570)无相关性。结论 PLVD与临床病理因素包括远处转移、淋巴结转移、Fuhrman细胞核分级及肿瘤T分期无相关性;ILVs的出现与远处转移、淋巴结转移及Fuhrman细胞核分级有显著的相关性。  相似文献   

11.
What's known on the subject? and What does the study add? Unlike most other cancers mutations of the p53 gene (TP53), typically indicated by increased p53 expression, are rare in renal cell carcinomas (RCC) and there is no evidence that mutation of TP53 is associated with outcome or treatment response. However, whilst TP53 mutations are not linked with outcome, p53 expression is as we show here. Our study is the first to demonstrate simultaneously that patients with increased p53 expression (significantly associated with MDM2 expression), have reduced disease specific survival even though the expressed p53 is rarely mutated. We therefore identify increased expression of wild‐type p53 and MDM2 in RCC as targets for future therapeutic approaches.

OBJECTIVE

  • ? To resolve much debated issues surrounding p53 function, expression and mutation in renal cell carcinoma (RCC), we performed the first study to simultaneously determine p53/MDM2 expression, TP53 mutational status (in p53‐positive patients) and outcome in RCC.

PATIENTS AND METHODS

  • ? In total, 90 specimens obtained from patients with RCC, who were treated by radical nephrectomy, were analyzed by immunohistochemistry for p53 and MDM2 on a tissue microarray, and p53 was functionally and genetically analyzed in p53 positive samples.
  • ? Outcome analysis was by the Kaplan–Meier method and univariate analysis was used to identify variables for subsequent multivariate analysis of correlations between clinical parameters and biomarker expression.

RESULTS

  • ? Up‐regulation of p53 in RCC is strongly linked with MDM2 up‐regulation (P < 0.001).
  • ? Increased coexpression of p53 and MDM2 identifies those patients with a significantly reduced disease‐specific survival by univariate (P= 0.036) and Cox multiple regression analysis (P= 0.027; relative risk, 3.20).
  • ? Functional (i.e. functional analysis of separated alleles in yeast) and genetic analysis of tumours with increased p53 expression shows that most patients (86%) retain wild‐type p53.

CONCLUSIONS

  • ? Coexpression of p53/MDM2 identifies a subset of patients with poor prognosis, despite all of them having organ‐confined disease.
  • ? Up‐regulated p53 is typically wild‐type and thus provides a mechanistic explanation for the association between p53 and MDM2 expression: up‐regulated wild‐type p53 likely promotes the observed MDM2 coexpression.
  • ? The results obtained in the present study suggest that the p53 pathway is altered in a tissue/disease‐specific manner and that therapeutic strategies targeting this pathway should be investigated to determine whether the tumour suppressive function of p53 can be rescued in RCC.
  相似文献   

12.
目的明确RCC5在肾透明细胞癌(ccRCC)组织中的表达水平及其对肾癌患者预后的影响。方法通过荧光定量PCR方法对54对ccRCC患者标本(包括癌组织和癌旁正常组织)的RCC5mRNA进行分析;并运用免疫组化对82对配对的癌组织和癌旁正常组织切片及161例癌组织切片进行染色;运用统计学方法分析RCC5的表达量和患者的临床特点之间关系。结果荧光定量PCR结果显示92.59%(50/54))的肾癌组织中RCC5表达水平明显高于癌旁正常组织(P〈0.001);82对癌组织及癌旁正常组织切片免疫组化显示,92.68%(76/82)的癌组织RCC5表达水平高于癌旁正常组织(P〈0.001);同时发现RCC5的表达水平与性别、肿瘤直径、病理分期、分级、TNM分期和复发率相关;RCC5高表达的患者预后一般较低表达者差,多元分析显示RCC5表达上调是ccRCC的独立预后因素。结论 RCC5的表达水平和ccRCC预后之间存在明显相关性;研究发现RCC5表达上调的患者预后较差,RCC5可能是一个新颖并且有临床价值的预后标志物。  相似文献   

13.
BackgroundClear cell renal cell carcinoma (ccRCC) is one of the most common urological malignancies, and once metastasis occurs, it often has a poor prognosis and lacks effective treatment. Therefore, there is an urgent need to screen some new biomarkers and explore their molecular mechanisms to improve the early clinical diagnosis and targeted therapy of ccRCC. SPOCK1 (SPARC/osteonectin, CWCV and Kazal-like domains proteoglycan 1) is a conserved multi-domain proteoglycan that plays an important role in the development of multiple cancer types; however, its prognostic value in ccRCC has not been investigated. The study of the prognostic value of SPOCK1 in ccRCC is a good complement to the study of ccRCC biomarkers.MethodsDatabases of this study included Oncomine, Kaplan-Meier Plotter, GEPIA, GeneMANIA, cBioPortal, and TIMER. Student’s t-test was used to analyze the differences in SPOCK1 expression in ccRCC tissues compared with tumor-adjacent normal tissues. Kaplan-Meier curves for survival analysis were used to assess the correlation between the expression of SPOCK1 and the prognostic outcomes. Correlation module drew the expression scatterplots between SPOCK1 and immune cell infiltration in ccRCC, together with the Spearman’s rho value and estimated statistical significance.ResultsThe SPOCK1 mRNA expression was significantly higher in ccRCC tissues (mean expression ± SD: 920.2±195.2) than in normal tissues (mean expression ± SD: 358.4±29.1, P=0.008), and high SPOCK1 expression significantly and positively correlated with the pathological stage of ccRCC patients (F value =10.2, P<0.001). Higher expression of SPOCK1 was also associated with significantly shorter overall survival (OS) and disease-free survival (DFS) in ccRCC patients (GEPIA: P=0.046, P<0.001, respectively; Kaplan-Meier Plotter: P=0.002, P=0.0022, respectively). The function of SPOCK1 is mainly related to tumor development and extracellular matrix remodeling, and it may participate in the epithelial-mesenchymal transition process. SPOCK1 expression significantly and positively correlated with infiltration of several immune cells in ccRCC, including cancer-associated fibroblasts (CAFs) (Rho =0.333, P=2.16×10−13), tumor-associated macrophages (TAMs) (Rho =0.18, P=1.02×10−4), and tumor-associated neutrophils (TANs) (Rho =0.165, P=3.83×10−4). Conversely, there was a significant and negative correlation between SPOCK1 expression and infiltration of CD4+ T cells (Rho =−0.113, P=0.015).ConclusionsSPOCK1 may be a potential prognostic biomarker in ccRCC.  相似文献   

14.
AIM: The objective of the present study was to characterize the clinicopathological features of histologically defined papillary renal cell carcinoma (RCC). METHODS: The present study included a total of 35 patients who were treated by radical surgery and subsequently diagnosed as having papillary RCC between April 1995 and June 2004. Clinicopathological data of these patients were retrospectively reviewed according to the previously reported classification system (Mod. Pathol. 1997; 10: 537-44). RESULTS: Of these 35 patients, 23 (65.7%) and 12 (34.3%) were diagnosed as type 1 and type 2 papillary RCC, respectively. Despite the lack of significant differences in clinical parameters between these two groups, including age, gender, clinical stage and metastasis, the incidence of symptomatic disease in patients with type 2 papillary RCC was significantly higher than that in those with type 1 papillary RCC. Pathological examinations demonstrated that there were no significant differences between these two groups in pathological stage, tumor grade or vascular invasion. Furthermore, there was no significant difference between these two groups in overall or recurrence-free survival. CONCLUSIONS: Although the present study included a small number of patients with short follow-up period, the clinicopathological features including prognoses were almost similar between patients with type 1 and type 2 papillary RCC; therefore, careful postoperative follow-up should be considered for patients with papillary RCC irrespective of morphological subtype.  相似文献   

15.
目的:探讨Dicer在肾透明细胞癌发生及转移中的作用。方法:选取正常肾小管上皮细胞株HKC、非转移性肾透明细胞癌细胞株769P、转移性肾透明细胞癌细胞株Caki-1以及36例肾透明细胞癌手术标本(其中11例已发生远处转移)和相应癌旁正常肾组织,应用实时定量PCR和Western blot方法检测Dicer在肾透明细胞癌细胞株和组织中mRNA和蛋白的表达情况,并分析Dicer的mRNA水平与临床病理资料的关系。结果:和正常肾小管上皮细胞株HKC相比;Dicer的mRNA水平在肾透明细胞癌细胞株769-P和Caki-1中均降低(P〈0.001),而转移性肾透明细胞癌细胞株Caki-1比非转移性肾透明细胞癌细胞株769-P表达水平更低(P〈0.001);和癌旁正常肾组织相比,Dicer的mRNA水平在‘肾透明细胞癌手术标本中明显降低(P〈0.001),且已发生远处转移的。肾癌标本比未发生远处转移的肾癌标本表达水平更低(P=0.04);Dicer在细胞株和组织中的蛋白水平的变化与mRNA水平的变化一致(P〈0.001);Dicer的mRNA水平在不同年龄、性别、组织学分级、肿瘤大小及T分期组间无统计学差异(P〉0.05)。结论:Dicer表达降低可能在。肾透明细胞癌的肿瘤发生中发挥作用,且其表达的进一步下降可能与肾透明细胞癌的远处转移有关。  相似文献   

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目的探讨滋养层糖蛋白5t4在肾透明细胞癌中的表达及其意义。方法采用免疫组织化学技术检测72例肾透明细胞癌组织标本、17例癌旁肾组织以及14例非癌因素的肾脏组织标本中5t4的表达,并对5t4在肾透明细胞癌的表达与组织学分级的关系进行分析。结果 5t4在肾细胞癌组织中的阳性率为70.8%,癌旁肾组织中的阳性率为41.2%,两者具有差异性(P0.05)。5t4在肾癌组织学分级中低分级与高分级的表达存在显著差异(P0.01)。结论 5t4可作为判断肾透明细胞癌分化程度的标志物。  相似文献   

18.
OBJECTIVE: To compare the outcomes of patients who had a elective partial nephrectomy (PN) or radical nephrectomy (RN) for clear cell renal cell carcinoma (RCC) of 4-7 cm. PATIENTS AND METHODS: From March 1998 to July 2004, 45 and 151 patients underwent PN and RN, respectively, for clear cell RCC. A multivariate Cox model was constructed for disease-free survival with adjustment for markers of disease severity, and a propensity-score approach used as a confirmatory analysis. RESULTS: In the PN and RN cohorts the treatment failed in one and 20 patients, respectively; the median follow-up was 21 months. The hazard ratio (95% confidence interval) for PN after adjusting for disease severity was 0.36 (0.05-2.82; P = 0.3). Using planned PN as a predictor (intent-to-treat analysis) the hazard ratio was 1.06 (0.32-3.53; P = 0.9). In the propensity-score model, planned PN was associated with a hazard ratio of 1.75 (0.50-6.14; P = 0.4). The serum creatinine level 3 months after surgery was significantly lower in patients who had PN, with a difference between the means of 0.36 (0.23-0.48; P < 0.001). CONCLUSIONS: Renal function was preserved after PN for 4-7 cm clear cell RCC tumours. When comparing the outcomes of PN and RN it is important to consider the intended operation as an independent variable. There was no clear evidence that PN was associated with worse cancer control, although a continued follow-up of this and other cohorts is warranted.  相似文献   

19.
《Urologic oncology》2015,33(2):68.e17-68.e23
ObjectivesTo evaluate the clinical use of recently published RNA-based molecular subtyping algorithms. Patients who undergo surgery for clinically localized clear cell renal cell carcinoma can experience very different outcomes, representing a longstanding challenge for the practicing urologist. Two recent publications suggest that molecular subtyping based on the expression of large panels of genes can help clinically localized clear cell renal cell carcinoma prognostication; however, the analyses was not adjusted for routinely collected clinicopathologic indices.Methods and materialsWe obtained level 3 RNA-seq RPKM data and corresponding clinicopathologic features from The Cancer Genome Atlas (TCGA) and assigned patients to the TCGA subtypes as well as to the ccA/ccB subtypes. To determine the prognostic ability of molecular subtyping after adjusting for variables that are collected as routine medical care, we used Cox models and adjusted for the composite Mayo stage, size, grade, and necrosis (SSIGN) score.ResultsBoth the TCGA and the ccA/ccB subtypes are significantly associated with tumor size, category, grade, and presence of necrosis. The association of these subtypes with overall survival is markedly attenuated following adjustment for the composite Mayo SSIGN score.ConclusionsBoth the TCGA and the ccA/ccB subtypes are associated with overall survival after adjusting for the Mayo SSIGN score. However, the effect sizes are similar to what has been reported for single markers, and thus the clinical use and cost-effectiveness of these RNA-based whole-genome signatures are questionable.  相似文献   

20.
目的:探讨E2F1在肾透明细胞癌中的表达及意义。方法:通过实时定量PCR和Western blot方法检测E2F1在肾透明细胞癌及对应瘤旁组织中mRNA和蛋白的表达情况,并分析E2F1的mRNA水平与临床病理资料的关系及表达相关性。结果:与对应瘤旁组织相比,E2FJ的mRNA水平在肾透明细胞癌手术标本中表达明显升高(P=0.0002),相应的蛋白水平对比与mRNA变化一致;E2F1的mRNA水平在不同年龄、性别组间差异无统计学意义(P〉0.05),而在组织学分级、肿瘤直径大小、T分期、临床分期和大血管浸润与否差异有统计学意义(P〈0.05)。结论:E2F1表达上调可能在肾透明细胞癌的肿瘤形成中发挥作用,且E2F1表达升高可能促进肾透明细胞癌的恶性进展。  相似文献   

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