肾透明细胞癌中Eotaxin-1的表达与肿瘤增殖能力相关

目的探讨嗜酸性粒细胞趋化因子-1 Eotaxin-1在肾透明细胞癌(ccRCC)中的表达情况及其与肿瘤增殖能力的关系。方法免疫组织化学检测58例肾透明细胞癌患者肾癌组织及癌旁组织中Eotaxin-1以及增殖细胞核抗原(PCNA)的表达并分析其与肾癌临床病理特征的关系;用Western blot法分析10例相互配对肾癌组织、癌旁组织中Eotaxin-1及PCNA的表达,并对Eotaxin-1与PCNA做相关性分析。结果 Eotaxin-1主要表达于胞质,PCNA主要表达于细胞核内,Eotaxin-1和PCNA在肾癌组织的阳性率明显高于癌旁组织(P0.05);病理分级为2-3级组的Eotaxin-1及PCNA阳性率显著高于病理分级1级组(P0.01)。临床分期为Ⅲ/Ⅳ组的Eotaxin-1及PCNA阳性率显著高于临床分期Ⅰ/Ⅱ组(P0.05),有淋巴结转移组的Eotaxin-1及PCNA阳性率高于无淋巴结转移组(P0.05);10例肾癌组织中Eotaxin-1及PCNA蛋白水平显著高于癌旁组织(P0.01,P0.05);Eotaxin-1与PCNA在肾癌组织中的表达存在相关性(P0.05)。结论肾透明细胞癌组织中Eotaxin-1与肾透明细胞癌的增殖能力密切相关,对Eotaxin-1的研究可能为临床对肾透明细胞癌诊断治疗提供新的思路。     

透明细胞肾细胞癌中cIAP1、cIAP2、XIAP的表达及其与临床指标的关系

目的：检测肾透明细胞癌中凋亡抑制蛋白cIAP1、cIAP2和xIAP基因表达状况及其与，临床病理指标间的关系。方法：采用RT-PCR方法检测cIAP1、cIAP2和XIAP在透明细胞肾细胞癌中RNA水平的表达。分析其与透明细胞肾细胞癌，临床病理指标间的关系。结果：在透明细胞‘肾细胞癌中cIAP1和cIAP2的mRNA阳性率分别为85％（17／20）和60％（12／20），均高于正常肾组织。cIAP1 mRNA在Fuhrman核分级1、2级的肾细胞癌中表达高于核分级3和4的肿瘤。XIAP的表达在肾细胞癌与癌旁正常肾组织间无差异，并与TNM分期、Fuhrman分级没有相关性。结论：IAP家族成员cIAP1与肾细胞癌的临床病理指标相关。     

EZH2和RUNX3在肾细胞癌中的表达及其临床意义

目的 检测EZH2和RUNX3蛋白在肾细胞癌中的表达,探讨它们与肾细胞癌临床病理特征间的关系,并分析它们的表达相关性.方法 利用免疫组织化学法分别检测肾细胞癌标本及对应的癌旁正常肾组织(各56例)中EZH2和RUNX3的表达情况,并利用统计学软件进行统计分析.结果 EZH2和RUNX3蛋白在肾癌组织中的阳性表达率分别为67.9％和37.5％,在癌旁正常肾组织的阳性表达率分别为28.6％和67.3％;EZH2和RUNX3在肾癌组织和癌旁正常组织中的表达差异均有统计学意义(P＜0.05),肾细胞癌中EZH2的高表达和RUNX3的低表达均与临床分期相关(P＜0.05),与病理分化程度、性别、年龄等的关系无统计学差异(P＞0.05).Spearman相关分析显示二者在肾癌中的表达没有明显的负相关关系.结论 EZH2和RUNX3可能共同参与了肾癌的发生发展过程,可成为肾癌的早期诊断及判断预后的指标.     

肾透明细胞癌组织中树突状细胞与微血管密度之间的关系

目的探讨树突状细胞(DC)的数量及成熟情况与肾透明细胞癌微血管密度(MVD)的相关性。方法收集解放军307医院2010-07/2013-01期间手术的30例肾透明细胞癌患者术后癌组织及癌旁标本,通过免疫组化检测石蜡切片中DC特异性标志CD11c、DC成熟标志MHC-Ⅱ和MVD标志CD34的表达情况并进行分析。结果 30例肾透明细胞癌患者中,癌组织中CD11c阳性率和MVD分别为(93.08±66.14)‰和26.31±11.05个明显高于癌旁组织(25.91±12.29)‰和12.78±5.49个,癌组织中MHC-Ⅱ阳性率为(9.65±3.61)‰明显低于癌旁组织(17.60±6.26)‰。MVD与MHC-Ⅱ阳性率成负相关关系,而与CD11c则无明显相关性。癌组织中各指标的表达与患者性别、年龄、TNM分期之间未见明显相关性。结论肾透明细胞癌癌组织中的血管密度、DC含量高于癌旁组织,而成熟DC含量低于癌旁组织,肿瘤微血管密度与DC成熟度之间存在负相关关系。     

肾细胞癌RASSF1A基因启动子区甲基化状况与表达水平研究

目的检测19例肾细胞癌患者癌组织及癌旁组织Ras相关区域家族蛋白1A（RASSFlA）基因启动子区甲基化情况并检测其mRNA表达水平，探索两者之间的联系。方法收集肾细胞癌患者癌组织及相应癌旁组织19份，分别提取其基因组DNA，以甲基化特异性PCR（Methylation special PCR，MSP）法检测RASSFlA基因启动子区甲基化情况。并以QPCR法检测了RASSFlA基因的mRNA表达水平。结果19例中有lO例肾细胞癌患者癌组织存在高甲基化，mRNA表达水平表达降低，二者之间存在显著负相关性（r=-0．8734，P〈0．01）。结论肾细胞癌中RASSFlA基因启动子区存在高甲基化，并抑制该基因的表达。     

P糖蛋白和谷胱甘肽—S—转移酶在肾细胞癌中的表达

探讨肾细胞癌与多药耐药的关系，方法：应用免疫组化方法，检测４例术前未进行化疗的肾细胞癌和１６例正常肾组织中的Ｐ糖蛋白和谷胱甘肽－２转移－π表达。结果：Ｐ－ａｇ和ＧＳＴ－π外地１６例正常肾组织中的表达率均匀１００％，在４４例肾细胞癌组织中分别为６３．６５和５４．５％Ｐｇ，Ｐ－ｇｐ和／或ＧＳＴ－π阳性表达率为７９．５％。     

肾细胞癌的临床病理与免疫表型研究

目的 研究肾细胞癌的临床病理特征、预后及免疫表型特点.方法 复习114例肾细胞癌的临床病理资料、HE切片,按2004年WHO肾肿瘤分类标准重新分类、随访并进行免疫组织化学染色.结果 114例.肾细胞癌包括5个类型,肾透明细胞癌77例(67.5%)、乳头状肾癌11例(9.6%)、肾嫌色细胞癌14例(12.3%)、Xp11.2易位_/TFE3基因融合相关性肾癌10例(8.8%)、未能分类肾肿瘤2例(1.8%).免疫组织化学结果,肾透明细胞癌主要表达CK(93.5%,72/77)、CD10(93.5%,72/77)、波形蛋白(75.3%,58/77),乳头状肾癌主要表达α-甲酰基辅酶A消旋酶(AMACR,11/11),肾嫌色细胞癌主要表达CD117(11/14),Xp11.2易位/TFE3基因融合相关性肾癌TFE3、AMACR、CD10和CK的阳性率分别为10/10、10/10、9/10和7/10.结论 肾癌是一组形态学上各有特征的异质性肿瘤,在形态学基础上,CD10、波形蛋白、CD117、AMACR、CK7、TFE3有助于亚型的诊断.     

KIT和RCC在肾嫌色细胞癌和透明细胞癌颗粒细胞亚型中鉴别诊断中的价值

肾嫌色细胞癌、透明细胞癌颗粒细胞亚型（GRCC）和肾嗜酸细胞瘤三者的鉴别在病理诊断中一直比较困难。作者应用免疫组化方法分别检测了11例肾嫌色细胞癌、12例肾嗜酸细胞瘤和6例GRCC中KIT、CDl0、RCC和RON的表达,并探讨了上述指标在这3种肾上皮性肿瘤中的鉴别诊断价值。结果发现KIT在肾嫌色细胞癌和肾嗜酸细胞瘤中100％表达,表达模式为胞质／胞膜阳性和胞质阳性,相反,     

肾透明细胞癌N-WASP蛋白表达特点及与临床病理相关性

目的研究肾透明细胞癌组织及癌旁正常肾组织中N-WASP表达特点及与临床病理的相关性。方法对73例肾透明细胞癌组织及癌旁正常肾组织行N-WASP免疫组织化学染色,比较两组表达差异。对癌组织N-WASP表达水平与肿瘤病理分级,临床分期进行相关性分析。对总体生存率行单因素及多因素预后分析。结果癌组织N-WASP表达低于癌旁组织表达(P0.001)。癌组织中N-WASP低、中表达的患者生存率高于高表达患者(P0.01)。癌组织N-WASP表达水平(P0.01)与患者总体生存率相关。癌组织N-WASP表达水平可以作为判断肾透明细胞癌预后的独立预测因素(P0.05)。结论 N-WASP在肾透明细胞癌中表达明显下降,并可以作为独立预测因素提示患者预后。     

透明细胞肾细胞癌组织中DNMT3B异构体表达及其整体甲基化的分析

目的检测透明细胞肾细胞癌组织中DNA甲基转移酶3B(DNA methyltransferase 3B,DNMT3B)异构体表达及其整体甲基化的变化,探讨这些变化与透明细胞肾细胞癌的关系。方法选取15例透明细胞肾细胞癌及其癌旁组织,应用Real-time PCR技术检测DNMT1、DNMT3A、DNMT3B与DNMT3B六种主要异构体的mRNA表达,应用Western blot法检验DNMT3B4蛋白表达;应用联合亚硫酸氢钠的限制性内切酶分析法(COBRA)分析重复序列Alu和LINE-1的甲基化水平。结果透明细胞肾细胞癌组织中DNMT3B4 mRNA和蛋白表达水平比癌旁组织高;重复序列Alu和LINE-1的甲基化水平在透明细胞肾细胞癌组织中比癌旁组织低。结论 DNMT3B4表达增加可能与整体甲基化降低及透明细胞肾细胞癌的发生有密切关系。     

High endogenous avidin binding activity: an inexpensive and readily available marker for the differential diagnosis of kidney neoplasms

It has been documented that some tissues, such as salivary gland, liver, cardiac and skeletal muscles and kidney, have high level endogenous biotin or endogenous avidin binding activity (EABA). Limited data is available on EABA in renal cell neoplasms. A tissue microarray (TMA) was constructed that included oncocytoma (n=30), chromophobe renal cell carcinoma (RCC) (n=18), clear cell RCC (n=45), clear cell RCC with granular/eosinophilic (G/E) features (n=19), papillary RCC (n=21), papillary RCC with G/E features (n=29) and benign renal tissues (n=31). The TMA slides were stained with or without biotin blocker and analyzed using the automated cellular imaging system (ACIS(R)). Without biotin blocker, a high positive rate of EABA was found in oncocytoma (56/60, 93%) and normal renal tubules (46/60, 77%). A moderate positive rate of EABA was found in clear cell and papillary RCCs with G/E features (13/39, 33% and 19/55, 35%, respectively). Chromophobe RCC and RCC without G/E features had essentially no EABA. With biotin blocker, benign renal tissue and clear cell RCC were negative for EABA; but a significant number of renal oncocytoma (29/60, 48%) and a few papillary RCC with G/E features (5/52, 10%) remained positive for EABA. In conclusion, high EABA may be used to differentiate oncocytoma from chromophobe RCC, and the staining results must be interpreted with caution when avidin-biotin detection system is used in diagnosing renal neoplasms.     

Differential expression of SHP2, a protein-tyrosine phosphatase with SRC homology-2 domains, in various types of renal tumour

SHP2, a widely distributed protein-tyrosine phosphatase with src homology-2 (SH2) domains, is highly expressed in the brain and may play a role in synaptic communications or cellular proliferation. In this study, we examined SHP2 protein expression in 110 renal cell tumours of various histological subtypes, including clear, granular, papillary, chromophobe, collecting duct, and sarcomatoid-type renal cell carcinoma (RCC), and oncocytoma. SHP2 was expressed predominantly in normal distal tubules and collecting ducts, and positivity in various types of renal tumours was as follows: clear cell RCC, 0% (0/77 cases); granular, 7.7% (1/13); papillary, 50% (3/6); sarcomatoid, 0% (0/1); chromophobe, 85.7% (6/7); collecting duct carcinoma, 0% (0/2); oncocytoma, 100% (4/4). Clear and granular-type RCCs showed a very low but positive expression of SHP2. Chromophobe RCC and oncocytoma showed the highest rates and strongest intensities of SHP2 protein on immunostaining. SHP2 may serve as a powerful marker in detecting rare tumours. Estimates of its expression may be useful in histological diagnosis.     

肿瘤标志物SURVIVIN及P27蛋白在肾细胞癌中表达的临床意义

目的：探讨新的凋亡相关基因Survivin蛋白和p27蛋白肿瘤标志物在人肾细胞癌中的表达及临床意义。方法：采用免疫组化SP法分别测定50例肾癌和12例正常肾组织中Survivin蛋白及p27蛋白的表达,并分析其与肾癌临床、病理的关系。结果：Survivin蛋白在肾癌组织中表达阳性率为68%（34/50）,而正常组织中未见表达,两者有统计学意义（P〈0.01）。肾癌中Survivin蛋白的表达与肾癌的病理分级呈正相关（P〈0.05）。而p27蛋白在正常肾组织中的阳性率为83.3%（10/12）,在肾癌组织中的阳性率为42%（21/50）,两者有统计学意义（P〈0.01）。p27蛋白表达与肾癌的分级呈负相关（P〈0.01）。结论：Survivin蛋白表达水平与肾癌的临床分期、淋巴结转移密切相关,且与p27蛋白呈负相关。联检Survivin蛋白和p27蛋白有助于提高对肾癌预后的评估,并可作为判定肾癌生物学行为的客观指标。     

肾癌病理组织中核转录因子κB的表达及其意义

目的：探讨核转录因子κB（NF-κB）表达在肾癌发生、发展中的意义。方法：采用免疫组化方法检测66例肾癌病理标本（肾癌组）中NF-κB的表达情况,并与40例非癌肾组织病理标本（对照组）中NF-κB的表达情况比较。结果：肾癌组NF-κB阳性表达率为75.8%,对照组NF-κB阳性表达率为15.0%,肾癌组明显高于对照组（P〈0.05）。NF-κB的表达与肾癌病理组织学分级之间无明显的相关性（P〉0.05）;NF-κB的表达与肾癌的TNM分期之间呈显著的正相关（P〈0.05）。结论：肾癌病程中存在NF-κB的异常激活,NF-κB的表达与肾癌病理组织学分级之间无明显的相关性;NF-κB的表达与肾癌的TNM分期之间呈显著的正相关关系。     

p53、c-erbB-2、PCNA和EGFR在膀胱癌中过表达及其意义

目的：研究癌基因和抑癌基因蛋白产物在膀胱移行细胞癌中异常表达与病理分级、临床分期、复发和预后的关系。方法：应用免疫组化Ｓ－Ｐ法检查１１７例膀胱移行细胞癌组织中ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ的表达水平。结果：１１７例膀胱移行细胞癌中ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ阳性表达率分别为４７．０％、２９．９％、５３．８％和４８．７％。ｐ５３和ＰＣＮＡ阳性表达产物定位于肿瘤细胞核内，ｃ－ｅｒｂＢ－２阳性表达产物定位于细胞膜上，ＥＧＦＲ阳性表达产物定位于细胞膜或细胞浆内。结果表明ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ异常表达与膀胱癌的分级、分期、复发及术后生存率等之间有统计学意义。结论：ｐ５３、ｃ－ｅｒｂＢ－２、ＰＣＮＡ和ＥＧＦＲ异常表达有助于评估膀胱癌预后，多基因异常表达作为预后评价指标更有意义。     

鼻咽癌细胞增殖因素的检测与预后的相关性

目的：探讨鼻咽癌细胞中细胞增殖因素cyclinD1、c-erbB-2、Ki-67、PCNA蛋白的表达及其与鼻咽癌预后的关系。方法：以免疫组化S－P法检测212例鼻咽癌组织cyclinD1、c-erbB-2,Ki-67和PCNA蛋白的表型。结果：cyclinD1蛋白表达阳性率81．25％,表达程度与临床分期、原发灶范围、鼻咽部复发呈正相关,与患者5年生存率呈负相关。c-erbB-2蛋白表达阳性率为95％,表达程度与临床分期、原发灶、颈部转移灶、局部复发及远处转移呈正相关,与5年生存率呈负相关。Ki-67蛋白表达阳性率为97％,表达程度与临床分期、原发灶、颈部转移灶呈正相关。PCNA蛋白表达阳性率为99％。在cyclinD1,c-erbB-2,Ki-67及PCNA4因素中除Ki-67与PCNA无明显相关性外,其他因素间均存在明显的相关性。多因素分析表明对鼻咽癌颈后有显著影响的因素是cyclinD1、c-erbB-2。结论：cyclinD1、c-erbB-2与鼻咽癌的预后有较好的相关性,对于cyclinD1、c-erbB-2高表达的患者,应采取综合治疗。     

The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the classification of renal cell carcinoma and renal oncocytoma: an immunohistochemical analysis of 328 cases

AIMS: To demonstrate the diagnostic utility of MOC31, BerEP4, renal cell carcinoma marker (RCC Ma) and CD10 in the classification of RCC and renal oncocytoma, based upon a comprehensive immunohistochemical analysis. METHODS AND RESULTS: Immunohistochemistry was performed on 328 samples consisting of 256 clear cell/conventional, 27 papillary, 28 chromophobe, five collecting duct, five unclassified RCCs and seven renal oncocytomas using antibodies MOC31, BerEP4 and antibodies against cytokeratins (KL-1, CAM5.2, 34betaE12, cytokeratin 7), RCC Ma, epithelial membrane antigen, E-cadherin, CD10, CD15 and vimentin. Multivariate analysis showed that MOC31, BerEP4, RCC Ma and CD10 have discriminatory value. MOC31 and BerEP4 chiefly labelled distal tubules of normal kidney while RCC Ma and CD10 labelled the proximal tubules. Twenty-three chromophobe RCCs (82%) were reactive for MOC31, while only four clear cell RCCs and three papillary RCCs were positive for this marker. Clear cell RCCs were characterized by a high positive rate for CD10 (82%) and a low positive rate for BerEP4 (27%). Papillary RCCs frequently coexpressed RCC Ma and BerEP4 (51%). All renal oncocytomas were negative for MOC31 and CD10. CONCLUSIONS: MOC31 has diagnostic merit in discerning chromophobe RCC. The CD10+/BerEP4- profile and RCC Ma+/BerEP4+ profile achieve moderate sensitivity and good specificity for clear cell RCC and papillary RCC, respectively. The non-reactivity for both MOC31 and CD10 is helpful in distinguishing renal oncocytoma from RCC. When properly selected, antibodies have immunohistochemical diagnostic utility for the classification of renal cortical epithelial tumours.     

Differential immunoprofiles of hepatocellular carcinoma, renal cell carcinoma, and adrenocortical carcinoma: a systemic immunohistochemical survey using tissue array technique.

The differential diagnoses of hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and adrenocortical carcinoma (ACC) are sometimes difficult due to their overlapping histologic features. Immunohistochemistry is a helpful adjunct in supporting the histologic diagnosis. In this study, the authors used the tissue array technique to systemically analyze the efficacy of different immunohistochemical panels in discerning these neoplasms. Immunohistochemical stains were performed on a total of 895 tumors (including 170 HCCs, 176 RCCs, and 40 ACCs) using monoclonal antibodies against hepatocyte antigen (HPA), CD10, RCC marker, vimentin, alpha-inhibin, keratins (KL-1, CAM 5.2, 7, and 20), epithelial membrane antigen, and polyclonal antibodies against carcinoembryonic antigen (pCEA) and alpha-fetoprotein, and antibodies Melan-A (A103), MOC31, and BG8. HPA immunostain alone detected 85.9% of HCCs, and the addition of canalicular pattern of pCEA and CD10 immunostains raised the sensitivity to 94.7%. RCC marker was positive in 54.5% of RCCs but was negative in all non-RCC tumors. Using positive CD10 and negative HPA and pCEA together with RCC marker increased the sensitivity to 74.4%. Immunoreactivity for alpha-inhibin and A103 could be detected in 67.5% and 55% of ACCs, respectively. When the two antibodies were combined, 82.5% of ACCs were labeled. Proper selection of immunohistochemical stains aid in the differential diagnosis of the three neoplasms. Using the tissue array technique, the authors also showed an effective model for comprehensive antibody testing.     

乳腺导管原位癌病理形态及c-erbB-2、p53和PCNA表达

目的：对乳腺导管原位癌进行病理形态分析，并行ｃ－ｅｒｂＢ－２、ｐ５３癌基因蛋白、增殖细胞核抗原（ＰＣＮＡ）表达以及相关性的研究，以期为临床判断潜在恶性程度及预后提供参考指标。方法：运用病理形态分析以及枸橼酸－微波－ＡＢＣ免疫组化法对２５例常规福尔马林固定、石蜡包埋乳腺导管原位癌组织进行回顾性研究。结果：（１）２５例乳腺原位导管癌ｃ－ｅｒｂＢ－２、ｐ５３、ＰＣＮＡ表达的阳性率分别为３６．０％，４０．０％和４０．０％；（２）粉刺型ｃ－ｅｒｂＢ－２、ｐ５３、ＰＣＮＡ表达的阳性率均高于非粉刺型，而且ｃ－ｅｒｂＢ－２阳性率相差有显著性（Ｐ＜０．０５）；（３）坏死、核异型性、核分裂数与ｃ－ｅｒｂＢ－２、ｐ５３、ＰＣＮＡ的表达有关，其中，坏死与ＰＣＮＡ阳性表达显著相关（Ｐ＜０．０５），核异型性与ｃ－ｅｒｂＢ－２蛋白表达显著相关（Ｐ＜０．０５）。结论：乳腺导管原位癌无论病理形态还是生物学行为都是异质性的，除了组织学亚型，某些形态指标以及ｃ－ｅｒｂＢ－２癌基因蛋白的表达也可作为恶性度指标。