卵巢交界性肿瘤中claudin-3和β-catenin的表达及临床病理意义

［摘要］ 目的 研究claudin-3和β-连环素 (β-catenin)蛋白在卵巢上皮性交界性肿瘤（borderline ovarian tumors,BOTs）组织中的表达及临床病理意义。方法 采用免疫组织化学SP法,检测57例BOTs中claudin-3和β-catenin蛋白的表达水平,并与17例正常卵巢组织、25例卵巢上皮性良性肿瘤、31例卵巢上皮性恶性肿瘤组织中claudin-3和β-catenin蛋白的表达水平进行比较。结果 与BOTs相比,claudin-3、β-catenin蛋白在卵巢癌组织中的阳性表达率均明显升高,而在良性肿瘤及正常卵巢组织中的表达率下降,差异均有显著性(P<0.01或P<0.05);而正常卵巢组织与良性肿瘤相比,差异无显著意义(P >0.05)。claudin-3、β-catenin蛋白的表达与BOTs临床病理分期、腹腔有无种植相关,而与组织学类型、患者年龄无关。claudin-3与β-catenin在BOTs组织中的表达呈正相关性(r=o.653, P=0.000)。结论 claudin-3与β-catenin在BOTs的发生、发展中起着协同而独立的作用,对其进行联合检测有助于BOTs的早期诊断、治疗,为BOTs的预后提供理论依据。     

claudin-3、4在食管鳞状细胞癌中的表达及其临床意义

目的:探讨claudin-3、4在人类食管鳞状细胞癌和癌旁正常组织中的表达及其临床意义。方法:应用免疫组织化学SP法检测54例食管鳞状细胞癌和26例癌旁正常组织中claudin-3、4的表达及其与临床病理参数的关系。结果:claudin-3在食管鳞状细胞癌中的阳性率(92.6%)显著高于癌旁正常组织(15.4%)(P<0.01),claudin-3的表达与性别、年龄、肿瘤大小、病理分级、TNM分期、淋巴结转移均无明显关系(P>0.05),但有远处转移者阳性率较无远处转移者低(P<0.05);而claudin-4在年龄≤ 60岁和有远处转移者阳性率均较年龄>60岁与无远处转移者低(P<0.01和P<0.05)。结论:claudin-3、4在食管鳞状细胞癌的发生中起着促进作用,但在有远处转移时出现表达缺失或低表达。     

Expression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma

The human aspartyl beta-hydroxylase is a highly conserved enzyme that hydroxylates epidermal growth factorlike domains in transformation-associated proteins. The aspartyl beta-hydroxylase gene is upregulated in many human malignancies. The purpose of this study was to investigate the expression of aspartyl beta-hydroxylase in hepatocellular carcinoma. Aspartyl beta-hydroxylase mRNA levels were measured in 161 hepatocellular carcinomas and paired nontumorous liver tissues by conventional and real-time RT-PCR. Immunohistochemical staining of aspartyl beta-hydroxylase was performed using EnVision Plus system. The results showed that aspartyl beta-hydroxylase was overexpressed in 150 of 161 hepatocellular carcinomas （93 %）, including 45 of 48 unifocal small hepatocellular carcinomas （94 % ）. Aspartyl beta-hydroxylase was highly expressed in hepatocellular carcinoma cells in contrast to its low level of expression in non-neoplastic liver cells. The protein expression level of aspartyl heta-hydroxylase in the hepatocellular carcinoma was parallel with the mRNA expression level （r=0. 659 4, P〈 0. 000 1）. A significantly higher tumor aspartyl beta-hydroxylase overexpression level was associated with the presence of intrahepatic metastasis and the progression of histological grades.     

Expression of β-catenin in renal cell carcinoma

Objective To investigate the expression of β-catenin and its mRNA in renal cell carcinoma.Methods Twenty-six cases with renal cell carcinoma (RCC) were studied by immunohistoche mistry, Western blot and RT-PCR.Results We found the expression of β-catenis is higher in cancer tissues than in norma l kidney tissues and the level of β-catenin is associated with the tumor stage . Its expression in tumor of pT3 and pT4 is obviously higher than pT1 and pT2 ( P&lt;0.01). That is to say, there was an overexpression of β-catenin protei n in RCC and its level was related to the tumor stage, but the expression of β -catenin mRNA had no difference between tumor tissue and normal tissue.Conclusion β-catenin may be related to the occurrence and progress of RCC.     

PIN1 Gene Overexpression and β-catenin Gene Mutation/Expression in Hepatocellular Carcinoma and Their Significance

The evolution of hepatocellular carcinoma (HCC) is a compound process which involves many kinds of genes and transductional pathways. The expression of the peptidyl-proplyl- isomerase PIN1 gene, the mutation in exon 3 of β-catenin and its correspondent abnormal expression and their roles in the hepatocellular carcinogeneisis were investigated. Among 29 pair cases of HCC and non-carcinoma tissues, the expression of PIN1 gene was detected by immunochemical staining. Mu-tations in exon 3 of β-catenin gene and differential expression of β-catenin gene were investigated by the methods of PCR-SSCP, direct sequencing and immunohistochemical technique as well. The re-sults indicated: (1) 44.8% (13/29) cases of HCC presented higher level of PIN1 gene expression than non-cancerous tissues (χ2 =32.63, P<0.05), especially in cytoplasm and nucleus, while there was lower level of PIN1 expression in non-cancerous tissues; (2) 58.6% (17/29) HCC tissues showed β-catenin protein accumulation in cytoplasm and nucleus. 46.2% (6/13) HCC tissues indicated β-catenin protein accumulation with higher level of PIN1 expression, while 53.8% (7/13) HCC tis-sues indicated β-catenin protein accumulation with lower level or trace of PIN1 expression (χ2 =0.00, P>0.05); (3) 24.1% (7/29) of primary tumor lesions carried gene mutations in exon 3 of β-catenin, and accompanied by β-catenin protein accumulation. There was no mutation in non-cancerous tissues. All the mutation presented in tissues with low level of PIN1 expression. There was no mutation of β-catenin gene in tissues with high PIN1 expression level (χ2=58.12, P<0.05). So it was postulated that the increase of PIN1 gene expression could promote hepatocellular carcinogenesis via a way dif-ferent from β- catenin gene mutation.     

Wnt／β-catenin信号转导通路与卵巢癌的相关研究

目的研究Wnt／β-catenin信号通路的枢纽分子β-连环素（β-catenin）及其下游靶基因c—Myc在卵巢癌中的表达。方法应用免疫组化S-P法检测60例卵巢癌、24例卵巢上皮良性肿瘤以及26例正常卵巢上皮组织中β-catenin和c-Myc的表达情况。结果β-catenin在卵巢癌组织的异位表达与正常卵巢组织相比,差异有统计学意义（P〈0．05）;β-catenin与卵巢癌的组织学分型以及分化程度具有相关性（P〈0．05）;c-Myc在卵巢上皮癌中表达分别与卵巢上皮良性肿瘤和正常卵巢上皮组织组相比,差异有统计学意义（P〈0．05）;c—Myc与卵巢癌分化程度相关（P〈0．05）;在卵巢癌组织中,β-catenin的异位表达与c—Myc的表达具有相关性（P〈0．05）。结论Wntβ-catenin信号通路可能是卵巢癌的发生途径。     

The expression and clinical sgnificance of Wnt3a, β-catenin and CyclinD1 in gastric carcinoma and gastric ulcers

目的:探讨Wnt3a、β-catenin、CyclinD1在胃癌和胃溃疡组织中的表达及其临床意义.方法:采用免疫组织化学S-ABC法检测48例胃癌组织及42例胃溃疡组织中Wnt3a、β-catenin、CyclinD1的表达及分布.结果:胃癌及胃溃疡组织中均未检测到Wnt3a的表达.β-catenin、CyclinDl在胃癌组织中表达较强,阳性反应与患者的年龄、性别、肿瘤的类型及TNM分期无关,平均光密度值为0.523 ±0.044及0.446±0.054,在胃溃疡组织中阳性反应的平均光密度值为0.367±0.073及0.311±0.029.β-catenin、CyclinD1在胃癌组织的表达明显高于胃溃疡组织,差异有统计学意义(P＜0.05).结论:胃癌组织中β-catenin、CyclinD1的表达明显高于胃溃疡组织,其表达与胃癌患者的年龄、性别、肿瘤的类型及TNM分期无关.     

Expression of βig- h3 in keratoconus and normal cornea

Objectives To observe the expression of βig- h3 in normal cornea and keratoconus and to elucidate the role of extracellular matrix in keratoconus.Methods In situ hybridization was used to detect the expression of βig- h3 in the cornea.The cDNA library was screened with human βig- h3 cDNA probe to locate βig- h3 mRNA in cells.Results Expression of βig- h3 was found mainly in the stroma of the normal cornea and keratoconus, but decrease depending on the degree of keratopathy.In some serious cases, no expression signal was detected. The strongest expression was seen at the border of the normal region and keratoconus.Conclusions βig- h3,the structural component of the extracellular matrix, can affect cell adhensiveness in the development of corneal fibrous interstitial organization.During the development of keratoconus, decreasing levels of βig- h3 cause the diminution of corneal steadiness, which is related to formation of keratoconus     

sirvivin和β-catenin在胆囊癌中的表达及意义

目的 探讨survivin和β-catenin在胆囊癌组织中的表达及意义.方法 应用免疫组织化学Envision法检测49例胆囊癌、15例胆囊腺瘤、15例慢性胆囊炎中survivin和β-catenin的表达情况.结果 胆囊癌中survivin的阳性表达率为83.67%(41/49),胆囊腺瘤、慢性胆囊炎中未见阳性表达,胆囊癌中survivin的阳性表达率显著高于后两组(P＜0.01).胆囊癌中β-catenin的异位表达率为61.22%(30/49),胆囊腺瘤为26.67%(4/15),慢性胆囊炎无表达,胆囊癌中β-catenin异位阳性表达率显著高于后两组(P＜0.05).结论 survivin和β-catenin的异位表达共同参与了胆囊癌的发生发展.     

结直肠肿瘤组织中β-catenin和c-myc的表达及其意义

目的 探讨β-catenin和c-myc在结直肠肿瘤中的意义.方法 用免疫组织化学技术检测非肿瘤结直肠组织、结直肠腺瘤组织和结直肠腺癌组织中β-catenin及c-myc.结果 β-catenin在非肿瘤结直肠组织、结直肠腺瘤组织和结直肠腺癌组织中异住异常表达率分别为8.0%、73.9%、96.2%,3组之间差异有统计学意义(P<0.05).非肿瘤结直肠组织、结直肠腺瘤组织和结直肠腺癌组织中c-myc表达的阳性率分别为4.0%、43.5%和76.9%,3组之间差异有统计学意义(P<0.05).结论 β-catenin异常表达及c-myc过度表达与结直肠肿瘤的发生有关,β-catenin异常表达可能与腺瘤的恶性转化易感性和结直肠腺癌的恶性行为有关,c-myc过度表达可能与结直肠肿瘤恶性化有关.     

原癌基因产物β-catenin在胃癌组织中的表达

探讨原癌基因产物β-catenin与胃癌发生、分型以及侵袭转移的关系。方法采用免疫组化SP法检测10例胃粘膜肠化生、10例不典型增生及49例胃癌标本中的β-catenin。结果β-catenin在正常胃粘膜和肠化生组织中表达均正常,在1例不典型增生组织中表达丢失,在胃癌组织中异常表达率为55.10％。浸润型胃癌异常表达率为69.69％,膨胀型25％(P<0.01)。无淋巴结转移者异常表达率为33.33％,淋巴结转移者64.71％(P<0.05)。无远处转移者50％,有远处转移者100％(P<0.05)。结论β-catenin与胃癌发生、Ming’s分型密切相关,是肿瘤获得高侵袭转移潜能的重要原因之一     

Expression of β-catenin protein in hepatocellular carcinoma and its relationship with alpha-fetoprotein

This study aimed to investigate the expression of β-catenin in hepatocellular carcinoma (HCC) tissues and its relationship with α-fetoprotein (AFP) in HCC. Immunohistochemistry was used to determine the expression of β-catenin in normal liver tissues (n=10), liver cirrhosis tissues (n=20), and primary HCC tissues (n=60). The relationship between β-catenin expression and clinical parameters of HCC was investigated. Real-time PCR and Western blotting were used to detect the mRNA and protein expression levels of β-catenin in the liver cancer cell line SMMC-7721 transfected with a plasmid encoding AFP, and also the mRNA and protein expression levels of β-catenin were measured in the liver cancer cell line Huh7 before and after the transfection with AFP shRNA plasmids. The results showed that β-catenin was only expressed on the cell membrane in normal liver tissues. Its localization to the cytoplasm and nucleus of cells was observed in a small proportion of cirrhotic tissues or adjacent HCC tissues, and such ectopic expression of β-catenin was predominant in HCC tissues. The abnormal expression of β-catenin was correlated with serum AFP levels, cancer cell differentiation and vascular invasion (P<0.05). Additionally, the increased expression of AFP resulted in the upregulation of β-catenin mRNA and protein levels, while knockdown of AFP with AFP shRNA led to significantly decreased β-catenin mRNA and protein levels (P<0.05). It was suggested that the abnormal expression of β-catenin is implicated in hepatic carcinogenesis and development. AFP can lead to increased expression of β-catenin, which may account for the poor prognosis of AFP-associated HCC patients.     

APC和β-catenin在大肠癌中的表达及其意义

目的 探讨APC和β-catenin在大肠癌发生、发展中的作用.方法 应用免疫组织化学方法检测30例正常大肠黏膜、30例大肠腺瘤、10例大肠腺瘤恶变及50例大肠癌组织中APC和β-catenin蛋白的表达情况.结果 大肠癌和大肠腺瘤恶变APC阳性率分别为44.0%、40.0%,显著低于大肠腺瘤的86.7%和正常大肠黏膜的100%,差异有统计学意义(P＜0.01).大肠癌、大肠腺瘤恶变和大肠腺瘤β-catenin胞浆/胞核异位表达率分别为62.0%、50.0%、30.0%,显著高于正常大肠黏膜的0%,差异有统计学意义(P＜0.01),大肠癌β-catenin异位表达率显著高于大肠腺瘤,差异有统计学意义(P＜0.01).大肠癌中β-catenin膜表达缺失率为46.0%,显著高于大肠腺瘤(10.0%)和正常大肠黏膜的0%,差异有统计学意义(P＜0.01),且与大肠癌组织分化程度、浸润深度、淋巴结转移、Dukes分期有关.APC蛋白表达与大肠癌组织分化程度有关.大肠癌中β-catenin异位表达与APC阳性表达呈负相关关系(r=-0.39,P＜0.05).结论 APC失表达和/或β-catenin异位表达与大肠癌的发生密切相关,可能是大肠癌发生的早期事件;β-catenin膜表达缺失与大肠癌的侵袭、转移有关.     

survivin和β-catenin在胆囊癌中的表达及意义

目的探讨survivin和β-catenin在胆囊癌组织中的表达及意义。方法应用免疫组织化学Envision法检测49例胆囊癌、15例胆囊腺瘤1、5例慢性胆囊炎中survivin和β-catenin的表达情况。结果胆囊癌中survivin的阳性表达率为83.67%（41/49）,胆囊腺瘤、慢性胆囊炎中未见阳性表达,胆囊癌中survivin的阳性表达率显著高于后两组（P〈0.01）。胆囊癌中β-catenin的异位表达率为61.22%（30/49）,胆囊腺瘤为26.67%（4/15）,慢性胆囊炎无表达,胆囊癌中β-catenin异位阳性表达率显著高于后两组（P〈0.05）。结论survivin和β-catenin的异位表达共同参与了胆囊癌的发生发展。     

β-catenin基因在肝细胞癌中的表达及意义

目的:研究β-catenin基因在肝细胞癌(HCC)中的表达情况并探讨其意义。方法:采用免疫组化S-P法检测56例肝细胞癌石蜡包埋标本中β-catenin的表达情况。结果:37例(66%)肝细胞癌β-catenin呈胞浆及胞核异位表达,29例(51.8%)呈胞膜减弱表达。β-catenin异位表达与肝细胞癌病理分级呈负相关(P<0.01),β-catenin胞膜减弱表达率在有癌栓形成及无包膜组显著高于无癌栓、有包膜组(P<0.05)。结论:β-catenin异常表达可能是肝细胞癌发生、浸润和转移的重要原因之一。     

FAK与β-catenin在子宫内膜癌中的表达及临床意义

目的：探讨粘着斑激酶（FAK）和pI连环素（β-catenin）在子宫内膜癌中的表达及临床意义。方法：采用免疫组织化学二步法,研究FAK和β-catenin在63例子宫内膜癌、30例正常子宫内膜组织中的表达情况。结果：FAK和β-catenin在子宫内膜癌组织中的阳性表达率分别为84．1％、63．5％,在正常子宫内膜组织中的阳性表达率分别为16．7％、13．3％,在子宫内膜癌组织中的表达均高于正常内膜组织（P〈O．05）。FAK与β-catenin的表达在不同肌层浸润深度、淋巴结转移及FIG0分期的子宫内膜癌中差异有统计学意义（P〈0．05）。β-catenin的表达在不同组织病理分级的子宫内膜癌中差异有统计学意义（P〈O．05）。在63例子宫内膜癌患者中,FAK与β-catenin的表达呈正相关（r=0．3653,P=0．0018）。结论：FAK和β-catenin在子宫内膜癌的侵袭与转移中起重要作用,二者的表达异常可以作为预测子宫内膜癌浸润转移及评估预后的指标。     

Wnt2、Wnt3a和β-catenin在硬皮病患者皮损中的作用

目的探讨Wnt/β-catenin信号通路异常活化在硬皮病（SD）发病机制中的作用及其与SD临床分型的关系。方法采用免
疫组织化学SP法检测45例SD患者［系统性硬化症（SSc）25例,局限性硬皮病（LSc）20例］皮损中Wnt2、Wnt3a及β-catenin的量
与分布,以20例健康成人皮肤作为正常对照（NC）。结果Wnt2、Wnt3a分别定位于SD患者皮损真、表皮胞浆和胞核,β-catenin
定位于真皮类成纤维细胞、外分泌腺上皮细胞及浸润淋巴细胞的胞核及NC、部分SD表皮细胞的胞膜;SD皮损中Wnt2胞浆着
色、Wnt3a及β-catenin核着色均显著高于NC（P<0.01）,而β-catenin膜着色则明显低于NC（P<0.01）;Wnt2、Wnt3a分别与
β-catenin核着色呈正相关（r=0.663,0.654,P<0.01）,而与β-catenin膜着色呈负相关（r=-0.532,-0.529,P<0.01）;SSc上述3种蛋白
的着色与LSc间的差异无统计学意义（P>0.05）。结论SD皮损中存在的异常活化的Wnt/β-catenin信号在其发病机制中可能起
重要作用;LSc和SSc分居于SD病谱的两端而非两种独立疾病。
     

Association of Serum Dkk-1 Levels with β-catenin in Patients with Postmenopausal Osteoporosis

Wnt signaling plays an important role in the bone development and remodeling. The Wnt antagonist Dkk-1 is a potent inhibitor of bone formation. The aims of this study were firstly to compare the serum Dkk-1 levels in postmenopausal osteoporosis patients with age-matched healthy controls, and secondly, to assess the possible relationship between Dkk-1 and β-catenin, sclerostin, or bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] in the setting of postmenopausal osteoporosis. A total of 350 patients with postmenopausal osteoporosis and 150 age-matched healthy controls were enrolled, and the serum levels of Dkk-1, β-catenin, sclerostin, OPG, and RANKL were detected by ELISA, and bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] were measured by Roche electrochemiluminescence system in two groups. Serum Dkk-1 levels were significantly higher in postmenopausal osteoporosis group than in control group(P<0.001). Univariate analyses revealed that serum Dkk-1 levels were weakly negatively correlated to β-catenin(r=–0.161, P=0.003) and OPG(r=–0.106, P=0.047), while multiple regression analysis showed a negative correlation between serum Dkk-1 levels with β-catenin(β=–0.165, P=0.009) and BMD(β=–0.139, P=0.027), and a positive correlation between serum Dkk-1 levels and CTX(β=0.122, P=0.040) in postmenopausal osteoporosis group. No similar correlations ware observed in control group. The results provided evidence for the role of Dkk-1 in bone metabolism and demonstrated the link of Dkk-1 and Wnt/β-catenin in some ways.     

结肠癌中Wnt/β-catenin信号通路与FAK关联性的初步研究

目的 研究β-连接素(β-catenin)和黏着斑激酶(FAK)在结肠癌中的表达及其临床病理参数的关系,探讨Wnt/β-catenin信号通路和FAK的关联性.方法 收集60例结肠癌组织标本和8例距病灶3～5 cm的癌旁正常肠黏膜组织标本,采用免疫组织化学技术检测两类标本中β-catenin和FAK的表达水平,将与其临床病理资料相结合进行综合分析.结果 正常β-catenin、异常β-catenin和FAK在结肠癌中的阳性表达率分别为66.7%(40/60)、63.3%(38/60)和73.3%(44/60),β-catenin表达和FAK的阳性表达与肿瘤的侵袭、转移密切相关,而与患者的年龄、性别和肿瘤的大小及分化类型均无关.β-catenin异常表达和FAK之间呈明显正相关(r=0.487,p=0.000).结论 β-catenin和FAK的表达与结肠癌的侵袭、转移和预后密切相关,Wnt/β-catenin信号通路和FAK之间存在正相关.