The oncogenic impact of RNF2 on cell proliferation,invasion and migration through EMT on mammary carcinoma

Mammary carcinoma (MC) is one of most common malignancy in women, and ring finger protein 2 (RNF2) possesses various roles in vast human tumors. In MC tissues as well as in cell lines RNF2 exhibited high expression, had significant association with tumor size, lymph node status, TNM stage, patients’ poor survival, and promoted cell proliferation, colony formation, cell migration and invasion of MC cell lines which was mediated by downregulation of E-cadherin protein. These data reveal that RNF2 protein plays a vital role in the development of MC and may be a potential therapy target of MC.     

The prognostic value of E-cadherin, α-, β- and γ-catenin in bladder cancer patients who underwent radical cystectomy

OBJECTIVES: To determine the value of the loss of expression of E-cadherin and cadherin associated molecules as useful markers for both prognosis and chemosensitivity in bladder cancer patients who have undergone radical cystectomy. PATIENTS AND METHODS: In 55 paraffin embedded specimens of radical cystectomy at our hospital from 1982 to 2000, the expression of E-cadherin, alpha-, beta- and gamma-catenin was examined by immunohistochemical staining. To evaluate the prognostic significance of these molecules, Kaplan-Meier survival curves were constructed and a statistical analysis was calculated by a log-rank test. A multivariate test (tumor stage, tumor grade, lymph node metastasis, configuration, the expression of E-cadherin, alpha-, beta- and gamma-catenin) was performed to detect prognostic markers. RESULTS: Normal expression was found in 33 cases (60.0%) for E-cadherin, 29 (52.7%) for alpha-catenin, 31 cases (56.4%) for beta-catenin, and 31 cases (56.4%) for gamma-catenin. The expression patterns for E-cadherin, alpha-, beta- and gamma-catenin were significantly correlated with each other (P < 0.01). Survival analysis showed a significant difference between normal and aberrant expression in each staining. A multivariate analysis revealed that the expression of alpha- catenin was an independent prognostic factor (P = 0.0191). In 23 patients that received adjuvant chemotherapy, there was a significant difference in survival between the normal and aberrant expression of alpha-catenin, but not other molecules. CONCLUSION: Alpha-catenin may not only be a good prognostic marker, but also one of key molecules that determine the chemosensitivities in patients with invasive bladder cancer.     

上皮型钙黏蛋白在子宫内膜癌中的表达

目的　探讨上皮型钙粘蛋白 (E cadherin ,E cad)在子宫内膜癌中的表达意义。方法　采用免疫组织化学方法检测 16例子宫内膜癌及 10例子宫肌瘤、卵巢囊肿患者 (对照组 )的E cad表达。结果　子宫内膜癌患者的E cad表达阳性率较对照组显著增高 (P <0 .0 5 )。子宫内膜癌E cad表达水平 :①与临床分期相关 ,临床早期表达显著高于晚期 (P <0 .0 5 ) ;②与肿瘤细胞分化程度相关 ,分化越差 ,表达越低 (P <0 .0 5 ) ;③与子宫肌层浸润深度成反比 ,浸润肌层越深表达越低 (P <0 .0 5 )。结论　E cad在子宫内膜癌的侵袭转移中发挥重要的作用 ,它的丢失是癌细胞发生侵袭性生长过程中的关键环节     

Loss of membranous E-cadherin expression in pancreatic cancer: Correlation with lymph node metastasis,high grade,and advanced stage

Epithelial cadherin (E-cadherin) is a Ca²⁺-dependent cell-cell adhesion molecule that connects cells via homotypic interactions. Its function is critical in the induction and maintenance of cell polarity and differentiation, and its loss of downregulation is associated with an invasive and poorly differentiated phenotype in colon and other tumours. We have used an avidin-biotin immunoperoxidase technique to localize E-cadherin in microwave-treated, paraffin-embedded sections from 36 patients with pancreatic adenocarcinomas. E-cadherin was expressed by normal ductal and acinar cells with typical membranous staining at the intercellular junctions. Loss of normal surface E-cadherin expression was found in 19/36 (53 per cent) tumours compared to the adjacent normal ductal cells. Abnormal E-cadherin expression was found more frequently in poorly differentiated (grade III) (6/7, 86 per cent) than in well-differentiated tumours (grade I) (4/14, 28 per cent) (P=0·012). Membranous E-cadherin expression was also lost more frequently in primary tumours with lymph node (stage III) (14/23, 61 per cent) and distant metastasis (stage IV) (2/2, 100 per cent) compared with 3/11 (27 per cent) lymph node-negative tumours (stage I) (P=0·043). In conclusions, our data indicate that loss of membranous E-cadherin expression is associated with high grade and advanced stage in pancreatic cancer.     

卵巢上皮性肿瘤中Skp2、p27kipl、E-cad的表达

目的检测Skp2、p27kipl和E-cad在卵巢上皮性肿瘤中的表达情况及其相互关系。方法采用免疫组化SP法，检测99例卵巢上皮性肿瘤组织中Skp2、p27kipl及E-cad的表达。结果p27kipl在卵巢良性肿瘤、交界性肿瘤的表达率分别为76．5％、70．6％高于卵巢癌29．2％（P〈0．05），在早期癌中的表达高于晚期癌（P〈0．05）。Skp2在卵巢良性肿瘤、交界性肿瘤的表达率分别为0、23．5％，均低于卵巢癌50．8％（P〈0．05），在早期癌的表达低于晚期癌（P〈0．05）。卵巢癌中skp2表达与组织分化有关，在低分化癌的阳性表达率高于高分化癌（P〈0．05），在组织学类型方面，浆液性癌中skp2的阳性表达率高于非浆液性癌（P〈0．05）。E—cad在良性肿瘤、交界性肿瘤和卵巢癌表达率分别为88．2％、82．4％、55．4％，恶性组低于良性组（P〈0．05）。E—cad在早期癌的表达率高于晚期癌（P〈0．05）。Skp2表达与p27kipl表达呈负相关（P〈0．05），E-cad表达与p27kipl表达呈正相关（P〈0．05），而E-cad表达与Skp2表达则呈负相关（P〈0．05）。结论skp2过度表达与p27kipl表达减少可能与卵巢上皮性肿瘤的发生发展密切相关，而E-cad在晚期卵巢癌中表达降低可能反映了卵巢癌分化程度的降低。     

大肠癌上皮型钙粘蛋白表达及其与浸润转移的关系

目的　探讨上皮型钙粘蛋白 (E cad)表达与大肠癌 (CLI)浸润转移的关系。方法　选取 6 0例原发性CLI组织及相应癌旁正常组织 ,用免疫组化SP法和抗E cad抗体检测观察E cad的表达。结果　CLI组织中E cad总阳性率 55% ,正常大肠上皮组织全部表达 ,E cad的表达与癌组织分化程度、生长方式、浸润深度、淋巴结转移密切相关 (P <0 .0 1)。结论　CLI组织E cad丧失或低表达是其获得浸润转移能力的因素之一。E cad可作为一种新的CLI标志物 ,其表达对判断预后有一定价值     

前列腺癌组织中ILK和E-Cadherin的表达及其意义

目的　探讨整合素连接激酶 (ILK )、上皮细胞钙黏素 (E cad)在前列腺癌组织中的表达及其意义。方法　应用免疫组织化学 (S P)方法检测 5 0例前列腺癌及 16例良性前列腺增生组织中ILK、E cad蛋白的表达。结果　前列腺癌组织中ILK、E cad阳性表达率分别为 46.0 % (2 3 /5 0 )、5 0 .0 % (2 5 /5 0 )。随肿瘤细胞病理分级、临床分期程度的增高 ,ILK阳性表达率增高而E cad表达降低 ,各组间均有显著性差异 (P <0 .0 5或P <0 .0 1)。与良性前列腺增生组织中的阳性表达率 10 0 .0 % (16/16)和 6.2 % (1/16)比较 ,均有显著性差异 (P <0 .0 5 )。结论　ILK、E cad蛋白异常表达在前列腺癌的恶性进展中起重要作用 ,ILK高表达或激活可能是E cad低表达或缺失的原因之一 ,联合检测ILK、E cad表达有利于判断病期及预后。     

Combined analysis of E-cadherin gene (CDH1) promoter hypermethylation and E-cadherin protein expression in patients with gastric cancer: implications for treatment with demethylating drugs.

BACKGROUND: Hypermethylation is studied as a new, relevant mechanism for silencing tumor suppressor genes. It is a potentially reversible epigenetic change and it is the target of novel anticancer compounds with demethylating activity. In this perspective, we investigated E-cadherin gene (CDH1) promoter hypermethylation in gastric carcinomas and its correlation with E-cadherin protein expression. METHODS: Consecutive cases of gastric carcinoma with assessable paraffin-embedded tumor blocks and paired normal mucosa were considered eligible for study entry. CDH1 promoter hypermethylation and E-cadherin protein expression were determined by methylation-specific polymerase chain reaction and immunohistochemistry, respectively. RESULTS: CDH1 promoter hypermethylation was found in 20 out of 70 gastric carcinomas and the epigenetic change occurred in the early, as well as in the locally advanced disease. In five cases, hypermethylation was also detected in the normal mucosa. Eighteen out of 20 hypermethylated tumors were of the diffuse histotype (P=0.0001). Of 24 tumors with reduced or negative E-cadherin expression, 19 were hypermethylated and 5 were unmethylated (P=0.0001). CONCLUSIONS: CDH1 promoter hypermethylation frequently occurs in gastric carcinomas of the diffuse histotype and it is significantly associated with downregulated E-cadherin expression. The knowledge on the hypermethylation status of tumor suppressor genes may be relevant to the development of demethylating drugs and novel chemopreventive strategies in solid tumors.     

钙粘附素及连环素表达与乳腺癌转移及预后的关系

目的:了解乳腺癌E-钙粘附素、连环素-α,-β的表达改变与转移及预后的关系。方法:采用免疫组织化学染色、病理组织学,对105例乳腺癌患者术后定期随访,统计学分析。结果:105例乳腺癌三种粘附分子组化染色减弱和消失频率为E-钙粘附素56%,连环素-α64%,连环素-β43%,与正常及非典型增生组差别明显,P值均小于0.001。单因素分析未能找到E-钙粘附素与转移及预后的联系,但证明连环素-α和-β表达下降分别与癌分化程度及与转移、预后相关,P<0.05和P<0.01。三种粘附分子中E-钙粘附素与连环素-α的表达有平行关系,双阳性组的转移率明显低于一种蛋白表达下降组,P<0.05。COX多因素分析三种粘附蛋白表达均未能成为独立影响乳腺癌预后的因素。结论:E-钙粘附素、连环素-α,-β表达的免疫组化反应在乳腺癌呈下降的总趋势,E-钙粘附素与连环素-α的表达有平行关系,双阳性者转移率明显低。在三者之中连环素-β表达下降与癌转移及病程进展有明显相关性,预后相对差。在考虑用细胞间粘附体系为判断乳腺癌预后指标时必须对该三种分子作综合检测。