环氧化酶2和血管内皮生长因子在透明细胞性肾细胞癌中的表达及其与血管生成的关系

目的 探讨透明细胞性肾细胞癌(CCRCC)组织中环氧化酶2(COX-2)和血管内皮生长因子(VEGF)的表达及其与血管生成的关系.方法 应用免疫组化Envision法,检测80例CCRCC和20例正常.肾组织中COX-2和VEGF的表达及CD34标记的微血管密度(MVD),结合临床病理特征进行综合分析,探讨CCRCC组织中COX-2和VEGF的表达与血管生成的关系.结果 在CCRCC组织和正常肾组织中均有COX-2和VEGF表达.80例CCRCC中,COX-2和VEGF表达阳性率分别为65.0%和61.3%,均明显高于正常肾组织(分别为10.0%和20.0%).80例CCRCC组织MVD为70.13±19.99,20例止常肾组织MVD为59.75±15.17,差异有统计学意义(P＜0.05).COX-2的表达与CCRCC组织学分级、TNM分期及淋巴结转移有关(P＜0.05).CCRCC组织中,COX-2的表达与VEGF的表达呈正相关(r=0.485),COX-2和VEGF的表达均与MVD正相关(r分别为0.851和0.736).结论 COX-2与CCRCC血管生成有关,VEGF可能是COX-2调节CCRCC血管生成的重要中介.     

肾透明细胞癌组织CXCR4表达及其临床意义的研究

目的:研究趋化因子受体(CXCR4)在肾透明细胞癌(CCRCC)中的表达及临床意义。方法:应用免疫组织化学SP法从蛋白水平检测42例CCRCC和10例正常肾组织CXCR4的表达,应用半定量RT-PCR从基因水平检测CXCR4mRNA的表达情况,并分析它们与病理分级、临床分期及淋巴转移等的关系。结果:免疫组织化学法检测表明,CXCR4在CCRCC组织的阳性表达率为78.5%,正常肾组织中未检测到CXCR4蛋白的表达,差异有统计学意义,χ2=18.249,P=0.000。42例CCRCC均有不同程度的CXCR4mRNA表达,35例CXCR4mRNA呈高表达,高表达率为83.3%。CXCR4表达与不同临床分期、病理分级及淋巴转移有关,P<0.05;CXCR4mRNA的表达与病理分级、淋巴转移呈正相关,P<0.05。结论:CXCR4在CCRCC中的高表达可能对肾癌的发生、发展起促进作用,CXCR4可能作为肾癌预后的重要参考指标。     

肾透明细胞癌组织Fibulin-3表达及其临床意义

目的 探讨Fibulin-3在肾透明细胞癌(clear cell renal cell carcinoma,CCRCC)中的表达及其临床意义.方法 收集中山大学附属第一医院2000-04-01-2007-04-01手术切除并经病理确诊的157例CCRCC患者的石蜡标本及相关临床病理资料.其中男10例,女56例,平均年龄51.7岁.制作组织芯片,应用免疫组织化学方法检测Fibulin-3蛋白的表达情况,根据评分结果将RCC患者分为Fibulin-3高表达和低表达两组,并分析其与患者多种临床参数的相关性.结果 Fibulin-3在157例CCRCC组织中的阳性表达率为100.0％,高表达58例,低表达99例.Fibulin-3蛋白表达与CCRCC患者的性别、年龄、肿瘤大小、Fuhrman分级和组织学类型等临床病理参数无相关性,P＞0.05.Kaplan-Meier生存分析显示,Fibulin-3高表达与肾癌患者的预后相关,P=0.003;多因素Cox回归分析表明,Fibulin-3是CCRCC患者生存时间的独立影响因素,HR=2.30,95％CI为1.278～4.140,P=0.005.结论 Fibulin-3高表达与CCRCC患者的不良预后相关,提示Fibulin-3是预测CCRCC患者预后的潜在分子标志.     

代谢综合征与肾透明细胞癌相关性研究

目的 代谢综合征(metabolic syndrome,MS)是一组临床症候群,MS及其相关组分与癌症发生发展及病理特征具有密切关系.本研究旨在分析MS及其相关组分与肾透明细胞癌(clear cell cenal cell carcinoma,CCRCC)分期、分级及肿瘤大小的相关性.方法 回顾性分析2013-01-01-2015-12-30于山西医科大学第一医院就诊且病理诊断为CCRCC的375例患者的临床资料,包括年龄、性别、身高、体质量、血压、空腹血糖、生化结果、病理分期分级和肿瘤大小等.计数资料采用x2检验,计量资料以(x)±s表示,组间比较采用t检验,多因素分析采用Logistic回归分析.结果 MS组56例患者,其中男性患者32例,女性患者24例;非MS组319例患者,其中男性患者206例,女性患者113例.男女患者比较,差异无统计学意义,P=0.287.MS组与非MS组相比,年龄、吸烟、饮酒等差异无统计学意义,P值分别为0.100、0.691和0.269;而BMI指数、收缩压、空腹血糖、TG、HDL-C等差异均有统计学意义,均P＜0.001.在病理特点方面,MS与非MS相比,CCRCC病理分期(P=0.018)、分级(P=0.026)及肿瘤大小(P=0.026),差异均有统计学意义.MS相关疾病与CCRCC分期分析,糖尿病(P＜0.001)、高血压(P=0.015)、血脂紊乱(P=0.006)与CCRCC的分期有关.结论 CCRCC合并MS者病理分期较高、分级较低、肿瘤更大,糖尿病、高血压和血脂紊乱都可增加CCRCC的病理分期.     

肾透明细胞癌中血小板衍生生长因子BB和微血管密度的检测及临床意义

目的 探讨肾透明细胞癌中血小板衍生生长因子BB (PDGF-BB)的表达以及CD34标记的微血管密度(MVD)与患者临床病理特征及预后的关系.方法 采用免疫组化SP法,检测CD34和PDGF-BB在100例肾透明细胞癌组织中的表达情况.结果 100例肾透明细胞癌组织中,CD34标记的MVD为(105.49 ±37.95)个／高倍视野.以均数为分界点,将100例肾透明细胞癌分为低MVD组(42例)和高MVD组(58例).低MVD组和高MVD组的MVD分别为(75.12±22.41)个／高倍视野和(135.86±22.91)个／高倍视野,差异有统计学意义(P ＜0.001).肾透明细胞癌的MVD与肿瘤的T分期、病理分级以及术后是否发生转移有关(均P＜0.05).PDGF-BB蛋白低表达38例,高表达62例.肾透明细胞癌中PDGF-BB蛋白的表达与肿瘤直径、T分期、病理分级以及术后是否发生转移有关(均P＜0.05).生存分析结果显示,高MVD和PDGF-BB蛋白高表达的肾透明细胞癌患者的预后明显优于低MVD和PDGF-BB蛋白低表达者(均P＜0.001).相关性分析结果显示,PDGF-BB蛋白在肾透明细胞癌中的表达与MVD呈正相关(r=0.461,P＜0.001).结论 在肾透明细胞癌中,MVD和PDGF-BB蛋白的表达越高,肿瘤的分级和分期越好,患者的生存时间越长.     

CIP2A在膀胱尿路上皮癌组织中的表达及其临床意义

目的 研究蛋白磷酸酶2A癌性抑制因子(cancerous inhibitor of protein phosphatase 2A,CIP2A)在膀胱尿路上皮癌组织中的表达及其与临床病理特征的关系,探讨其成为膀胱尿路上皮癌预后指标的可行性.方法 应用RT-PCR和Western blot检测CIP2A mRNA和蛋白在25例膀胱尿路上皮癌和对应癌旁组织中的表达情况;应用组织芯片技术和免疫组织化学方法,检测CIP2A在117例膀胱尿路上皮癌和30例癌旁组织中的表达情况,分析CIP2A与膀胱尿路上皮癌患者临床病理特征及预后之间的关系.结果 CIP2A mRNA和蛋白在25例配对膀胱尿路上皮癌组织中的表达水平明显高于癌旁组织.免疫组织化学检测发现,膀胱尿路上皮癌组织中CIP2A蛋白的阳性表达率为76.9％(90/117),明显高于癌旁组织的6.7％ (2/30),差异有统计学意义(P＜0.001).CIP2A表达与肿瘤病理分级(P＜0.001)、临床分期(P＜0.001)、肿瘤大小(P=0.002)和淋巴结转移(P=0.046)有关,但与年龄、性别及肿瘤数目无关(P＞0.05).KaplanMeier单因素分析显示,CIP2A蛋白高表达是总体生存率和无复发生存率的影响因素(P＜0.001).Cox多因素风险比例模型显示,与总生存率相关的独立预后因素为临床分期、肿瘤病理分级和CIP2A表达,与无复发生存率相关的独立预后因素亦为临床分期、肿瘤病理分级和CIP2A表达.结论 CIP2A蛋白在膀胱尿路上皮癌组织中高表达,可能与膀胱尿路上皮癌的进展有关,其表达状态是膀胱尿路上皮癌患者独立预后因素.     

HIF-1 α、VEGF和pVHL在肾透明细胞癌中的表达及意义

[目的]探讨HIF-1α、VEGF和pVHL在肾透明细胞癌（clearcellrenalcellcarcino-ma．CCRCC）中的表达水平及与临床病理特征的关系。[方法]采用免疫组化法检测55例CCRCC中HIF-lα、VEGF和pVHL3种蛋白的表达,并对其与临床分期、病理分级、淋巴结转移及预后关系作相关性分析。[结果]52例获得随访,5年内共有12例死亡。HIF-1α和VEGF在55例CCRCC中阳性表达率分别为58．2％,100．0％,OT;RT4期组强表达率（72．7％、54．5％）显著高于pTl／pT2期组（29．5％、20．5％）（P〈0．05）;高级别组（75．0％、41．7％）显著高于低级别组（27．9％、23．3％）（P〈0．05）;两者高表达与淋巴结转移及中位生存时间密切相关（P〈O．05）,且两者表达存在正相关关系（r=-0．37,P〈0．05）。pVHL阳性表达率为52．7％（29／55）,与病理分级、临床分期、淋巴结转移及HIF-lα均无明显相关性（P〉O．05）。[结论]HIF．10t和VEGF在肾透明细胞癌中的表达可作为预测患者预后的指标,共同强表达预示生存时间短,对临床早期十预治疗具有重要的指导意义。     

CTGF、VEGF在卵巢癌中的表达及临床意义

目的 研究结缔组织生长因子(CTGF)、血管内皮生长因子(VEGF)的表达在卵巢癌发生、发展中的作用及临床意义.方法 采用免疫组化法检测92例卵巢癌组织和11例正常卵巢组织中CTGF和VEGF的表达,比较CTGF、VEGF在卵巢癌中表达的关系,并分析其在卵巢癌发生、发展中的临床意义及对预后的影响.结果CTGF在卵巢癌组织中的阳性表达率为19.6%,明显低于正常卵巢组织的81.8%(P﹤0.001);VEGF在卵巢癌组织中的表达率为89.1%,明显高于正常卵巢组织的27.3%(P﹤0.001).CTGF的阴性表达与卵巢癌患者的FIGO分期及淋巴结转移有关(P﹤0.05),但与患者的年龄及病理分级无关(P﹥0.05);VEGF的阳性表达与卵巢癌患者的淋巴结转移有关(P﹤0.05),但与患者的年龄、病理分级及FIGO分期无关(P﹥0.05).CTGF与VEGF在卵巢癌组织中的表达呈负相关(r=-0.444,P﹤0.05).结论 CTGF和VEGF的表达可能与卵巢癌的发生、发展及预后密切相关.     

HIF-1α、Glut-1在乳腺癌中的表达及其临床意义

目的:探讨HIF-1α、Glut-1在乳腺癌中的表达及其临床意义,并分析两者的相关性.方法:用免疫组化法检测60例乳腺癌癌组织中HIF-1α、Glut-1的表达,并分析其与临床病理因素的关系.结果:HIF-1α、Glut-1在乳腺癌组织中的阳性率分别为68.3%、63.3%.两者阳性表达与患者年龄、月经状态、肿瘤大小无相关性(P＞0.05).HIF-1α蛋白阳性表达率与病理分期、淋巴结有无转移、组织病理学分级有关(P＜0.05) .Glut-1阳性表达率与病理分期、淋巴结有无转移有关(P＜0.05),而与组织病理学分级无关(P＞0.05),但随组织病理分级增高有增高趋势.HIF-1α蛋白、Glut-1蛋白表达呈正相关(r=0.461, P ＜0.001).结论: HIF-1α、Glut-1蛋白的异常表达与乳腺癌的发生、发展及预后有关.     

膀胱癌中CHK1和RAD51的表达及临床意义

目的 探讨细胞周期检测点激酶1 (cell cycle checkpoint kinase 1,CHK1)及DNA双链断裂修复蛋白RAD51在膀胱癌中的表达及意义.方法 采用免疫组织化学法检测104例膀胱癌组织和40例癌旁正常膀胱黏膜组织中CHK1及RAD51蛋白表达,并分析其与膀胱癌临床病理特征的关系.结果 膀胱癌组织中CHK1及RAD51蛋白表达均高于癌旁正常膀胱黏膜组织(均P ＜0.05).CHK1蛋白表达在膀胱癌的病理组织学分级、病理分期方面差异均有统计学意义(均P＜0.05),而在性别、年龄、肿瘤直径、单发/多发以及初发/复发方面差异均无统计学意义(均P＞0.05).RAD51蛋白表达在膀胱癌的病理组织学分级方面差异有统计学意义(P＜0.05),在病理分期、性别、年龄、肿瘤直径、单发/多发以及初发/复发方面差异均无统计学意义(均P＞0.05).膀胱癌组织中CHK1和RAD51蛋白表达呈正相关(r=0.223,P＜0.05).CHK1蛋白阴性表达组预后好于阳性表达组(P＜0.05),而RAD51蛋白表达阴性组和阳性组预后比较差异无统计学意义(P＞0.05).结论 CHK1和RAD51蛋白在膀胱癌组织中呈高表达,二者在膀胱癌发生、发展中起重要作用,并与膀胱癌的病理组织学分级及预后密切相关.     

Suppression of MMP-9 activity by NDRG2 expression inhibits clear cell renal cell carcinoma invasion

Members of the NDRG (N-Myc downstream-regulated) gene family have been shown to play a variety of roles in human malignancies. Recently, it was shown decreased expression in clear cell renal cell carcinoma (CCRCC) and inhibited cell proliferation, but the role of the NDRG2 in CCRCC invasion has not been described. We examined the expression of NDRG2 protein in CCRCC samples and the association between NDRG2 expression and CCRCC patients survival. Real-time RT-PCR and immunohistochemical analysis were used to measure NDRG2 expression in 60 paired CCRCC and adjacent normal tissues. Changes in cell invasion were detected by up- or down-regulating NDRG2 by adenovirus or siRNA. We found that NDRG2 expression is significantly down-regulated in CCRCC at mRNA and protein levels in a manner negatively associated with aggressive tumor behaviors, such as TNM stage (P?=?0.003), Fuhrman??s grade (P?=?0.024), tumor invasion (P?=?0.001) and tumor recurrence (P?=?0.004), as well as shorter patient survival rates (P?=?0.0041). Furthermore, NDRG2 could suppress CCRCC cell invasion through regulating MMP-9 expression and activity. So, these results suggest that NDRG2 can inhibit extracellular matrix-based tumor cell invasion and thereby play important roles in suppressing tumor metastasis in CCRCC. NDRG2 expression may also be a significant prognostic indicator for CCRCC.     

T1期肾透明细胞癌CT强化特征参数与Fuhrman病理分级的相关性分析

目的探讨T1期肾透明细胞癌(CCRCC)的CT强化特征参数与Fuhrman病理分级之间的相关性。方法选取2015年4月至2019年4月间北京市昌平区中西医结合医院收治的67例T1期CCRCC患者,整理并分析其CT强化图像,根据术后病理Fuhrman核分级分组,其中Ⅰ~Ⅱ级患者作为甲组,Ⅲ~Ⅳ级患者作为乙组。观察不同分级患者CT平扫、强化参数中的始增时间(AT)、达峰时间(TTP)和峰值强度(PI),并分析与Fuhrman病理分级之间的相关性。结果CT平扫和强化显示,甲组患者CT值高于乙组,差异有统计学意义(P<0.05)。Pearson相关分析结果显示,CT平扫、高强化区皮质期、高强化区髓质期、低强化区皮质期和低强化区髓质期等参数均与Fuhrman核分级呈负相关,差异均有统计学意义(均P<0.05)。结论T1期CCRCC患者的CT强化特征参数与Fuhrman病理分级存在一定相关性,对CCRCC早期诊断和治疗具有重要参考价值。     

术前外周血淋巴细胞与单核细胞比值和白蛋白在肾透明细胞癌预后评估中的价值

背景与目的：越来越多的证据提示炎症在肿瘤的发展演进中起着重要的作用,术前外周血淋巴细胞与单核细胞比值（lymphocyte-to-monocyte ratio,LMR）和白蛋白被证明是各种肿瘤的独立预后因素。探讨LMR和白蛋白在传统临床预后预测模型的基础上对肾透明细胞癌（clear cell renal cell carcinoma,ccRCC）预后评估的应用价值。方法：回顾性分析2012—2015年在广西医科大学第一附属医院行RCC根治术或肾部分切除的147例ccRCC患者的临床资料。外周血LMR和白蛋白于术前1周收集,LMR采用中位数3.42,白蛋白用40 g/L作为截点。采用单因素分析和COX回归模型,分析LMR和白蛋白及其他临床因素与患者预后的关系。将LMR和白蛋白结合传统预测指标TNM分期及Fuhrman分级进行分析。采用C指数预测LMR和白蛋白对RCC预后的准确性;同时,采用LMR、白蛋白、TNM分期和Fuhrman分级构建列线图,预测患者的生存率。结果：术前低LMR和低白蛋白是患者总生存期（overall survival,OS）的独立危险因素（P=0.001和P＜0.001）。低LMR与高Fuhrman分级（P=0.006）和肿瘤坏死（P=0.039）密切相关;低白蛋白与高Fuhrman分级（P＜0.001）和高Mayo临床分期、大小、分级和坏死（stage, size, grade and necrosis,SSIGN）分数（P=0.001）有关。单因素分析提示LMR、白蛋白、TNM分期、Fuhrman分级、肿瘤大小、肿瘤坏死与OS相关;COX回归模型提示LMR和白蛋白是OS的独立预后因素（HR=0.370,95% CI：0.145~0.942,P=0.037;HR=0.325,95% CI：0.136~0.775,P=0.011）。将LMR和白蛋白结合传统预测指标TNM分期及Fuhrman分级进行分析后,C指数上升;列线图构建结果发现可以预测RCC患者术后3和5年的生存率。结论：术前外周血LMR和白蛋白是ccRCC患者术后的独立预后因素,将其纳入常规的临床病理学参数中,可以提高ccRCC患者术后预后评估的精准性。     

Percentage of high-grade carcinoma as a prognostic indicator in patients with renal cell carcinoma

BACKGROUND: The prognostic value of Fuhrman nuclear grade for patients with renal cell carcinoma has been well-characterized. However, to the authors' knowledge, the prognostic significance of the amount of high-grade renal cell carcinoma has not been previously analyzed. METHODS: The authors identified 898 consecutive renal cell carcinoma cases treated with nephrectomy between 1989 and 2003. Histopathologic features that were captured based on re-review of all slides included histologic type, pathologic stage, conventional Fuhrman grade, and percentage of Fuhrman grade 3 and 4 carcinoma, as ascertained by visual inspection of histologic slides. The clinical endpoints were metastasis-free survival, cancer-specific survival, and overall survival. RESULTS: Kaplan-Meier analysis demonstrated that both conventional Fuhrman grading and the percentage of Fuhrman grade 3 and 4 carcinoma were highly correlated with all 3 measures of patient survival (P < .0001). The creation of 3 categories of the percentage of Fuhrman grade 3 and 4 carcinoma (0%, 1-50%, and 51-100%) generated distinctly separate survival curves. On Cox proportional hazards multivariate analysis, TNM stage, tumor size, and the percentage of Fuhrman grade 3 and 4 carcinoma were all found to be significantly associated with all 3 types of patient survival (all P values <.05). CONCLUSIONS: The determination of the percentage of renal cell carcinoma that is 0%, 1% to 50%, or 51% to 100% high Fuhrman grade 3 and 4 is a simple and powerful measurement of patient outcome after surgery that provides additional prognostic information beyond stage, tumor size, and conventional Fuhrman grade. This prognostic information could be useful in the stratification of patients into prognostic groups for the development of more individualized follow-upschedules and for enrollment into clinical trials.     

Osteopontin expression correlates with prognostic variables and survival in clear cell renal cell carcinoma

BACKGROUND AND OBJECTIVES: Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including tumorigenesis and tumor cell metastasis. Recently, it has been detected in a growing number of human tumors, and assessed as a potential prognostic marker. The aim of this study was to analyze the expression of OPN in normal renal tissue and clear cell renal cell carcinomas (CRCCs), and to assess its prognostic significance. METHODS: The expression of OPN protein was immunohistochemically analyzed in 171 CRCCs and compared to usual clinicopathological parameters such as tumor size, nuclear grade, pathological stage, Ki-67 proliferation index, and cancer-specific survival. RESULTS: In normal renal parenchyma, the expression of OPN was seen in distal tubular epithelial cells, calcifications, and some stromal cells. The upregulation of OPN was observed in 61 CRCCs (35.7%) in the form of cytoplasmic granular staining of various intensities. Statistical analysis showed correlation of the OPN expression with tumor size (P < 0.001), Fuhrman nuclear grade (P < 0.001), pathological stage (P = 0.011), and Ki-67 proliferation index (P < 0.001). Moreover, patients with OPN-positive tumors had significantly worse prognosis in comparison to patients with tumors lacking OPN protein (P = 0.004). CONCLUSION: Our results suggest that overexpression of OPN is involved in the progression of CRCC.     

环氧合酶-2、血管内皮生长因子在透明细胞性肾细胞癌中的表达及其与肿瘤发生、发展的关系

目的探讨环氧合酶-2（COX-2）、血管内皮生长因子（VEGF）表达与透明细胞性肾细胞癌（CCRCC）患者预后的关系。方法应用免疫组织化学EnVision法检测80例CCRCC患者肿瘤组织和20例输尿管癌或肾盂癌患者正常肾组织中COX一2、VEGF的表达情况,结合临床病理参数分析二者与CCRCC患者预后的关系。结果COX-2在CCRCC组织中的阳性表达率为65．00％（52／80）,显著高于正常肾组织中的10．00％（2／20）（x^2=7．760,P=0．021）;VEGF在CCRCC中的阳性表达率为61．25％（49／80）,高于正常肾组织中的20.00％（4／20）（X^2=8．870,P=0．012）。COX-2的表达和CCRCCTNM分期（X^2=8．200,P=0．005）、组织学分级（X^2=13．860,P=0．000）以及淋巴结转移（X^2=6．050,P=0．001）有相关性,而与年龄（X^2=0．560,P=0．663）和肿瘤大小（x^2=0．700,P=0．528）无相关性;CCRCC组织中COX-2和VEGF的表达呈正相关（r=0．485,P〈0．01）。COX-2、VEGF的表达和CCRCC患者预后相关（分别为X^2=18．280,P=0．038;X^2=6．420,P=0．042）。结论COX-2和VEGF在CCRCC组织中的表达与肿瘤的发生、发展及预后密切相关,可以作为CCRCC患者的预后指标。     

Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience.

PURPOSE: To analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience. PATIENTS AND METHODS: Four thousand sixty-three patients from eight international centers were included in this retrospective study. Histologic subtype (1997 International Union Against Cancer [UICC] criteria of tumor response), age, sex, TNM stage, Fuhrman grade, tumor size, Eastern Cooperative Oncology Goup performance status (ECOG PS), and overall survival were determined in all cases. The prognostic values of clear cell, papillary, and chromophobe histologic features were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively. RESULTS: Clear cell, papillary, and chromophobe carcinomas accounted for 3,564 (87.7%), 396 (9.7%) and 103 (2.5%) cases, respectively. In univariate analysis, a trend toward a better survival was observed when clear cell, papillary, and chromophobe histologies were considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, Fuhrman grade and ECOG PS, but not histology, were retained as independent prognostic variables (P < .001). CONCLUSION: The stratification in three main renal cell carcinoma histologic subtypes as defined by the 1997 UICC-American Joint Committee on Cancer consensus should not be considered a major prognostic variable comparable to TNM stage, Fuhrman grade and ECOG PS.     

Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma

We attempted to describe, in a series of clear cell renal cell carcinoma (RCC), the relationship between CAIX expression, VHL gene mutations, tumor characteristics and outcome. Radical nephrectomy was performed in 100 patients. Genomic DNA was extracted from frozen tumor samples. Four amplimers covering the whole coding sequence of the VHL gene were synthesized by PCR and sequenced. The monoclonal antibody M75 was used to evaluate CAIX protein expression immunohistochemically. VHL mutations were identified in 58 patients (58%) and high CAIX expression (>85%) was observed in 78 (78%). Tumors with VHL mutation showed higher CAIX expression than those without (p = 0.02). Low CAIX expression and absence of VHL mutation were associated with a more advanced tumors e.g., higher T stages and presence of metastases. VHL mutation and high CAIX expression predicted longer progression-free survival (p = 0.037) and disease-specific survival (p = 0.001), respectively. In combination, they defined three prognostic groups (p = 0.002): (i) good prognosis, defined as VHL mutation and high CAIX (2-year survival: 86%), (ii) intermediate prognosis with either VHL mutation or high CAIX (69%), and (iii) poor prognosis with no VHL mutation and low CAIX (45%, median survival 18 months). CAIX expression, but not VHL mutational status, was an independent prognostic factor in multivariate analysis. Taken together, CAIX expression and VHL mutational status are able to stratify patients with clear cell RCC into distinct groups with regards to clinicopathological variables and prognosis, with low CAIX expression and absence of VHL mutation being associated with a poor clinicopathological phenotype and diminished survival.     

The relationship between the preoperative systemic inflammatory response and cancer-specific survival in patients undergoing potentially curative resection for renal clear cell cancer

The relationship between tumour stage, grade (Fuhrman), performance status (ECOG), a combined score (UCLA Integrated Staging System, UISS), systemic inflammatory response (elevated C-reactive protein concentration), and cancer-specific survival was examined in patients undergoing potentially curative resection for renal clear cell cancer (n=100). On univariate survival analysis, sex (P=0.050), tumour stage (P=0.001), Fuhrman grade (P<0.001), UISS (P<0.001), C-reactive protein (P=0.002) were significant predictors of survival. On multivariate analysis with sex, UISS and C-reactive protein entered as covariates, only UISS (HR 2.70, 95% CI 1.00-7.30, P=0.050) and C-reactive protein (HR 4.00, 95% CI 1.21-13.31, P=0.024) were significant independent predictors of survival. The presence of a preoperative systemic inflammatory response predicts poor cancer-specific survival in patients who have undergone potentially curative resection for renal clear cell cancer.