The Wnt pathway, epithelial-stromal interactions, and malignant progression in phyllodes tumours

In a previous study of phyllodes tumours, it has been shown that both the stroma and the epithelium can exhibit distinct molecular changes, suggesting that both are part of the neoplastic process. In view of this finding, it was decided to study stromal-epithelial interactions in these tumours by examining the Wnt-APC-beta-catenin pathway. Beta-catenin and cyclin D1 immunohistochemistry was performed on 119 phyllodes tumours. Eighty-six (72%) showed stromal nuclear beta-catenin localization and in 57% the staining was moderate or strong; however, of the eight malignant tumours in the series, seven showed absent or weak nuclear staining (p<0.025). In no tumour was nuclear beta-catenin staining seen in the epithelial component. Moderate or strong stromal cyclin D1 staining correlated with nuclear stromal beta-catenin staining (p<0.05). Forty-five of the tumours, including two malignant lesions, were screened for beta-catenin exon 3 mutations using SSCP and sequencing, but none was found. Loss of heterozygosity (LOH) of the marker D5S346 was used to infer APC mutation, but only one (benign) tumour showed LOH. Wnt2 and Wnt5a mRNA was localized by in situ hybridization in 13 cases (three malignant) chosen to reflect the different beta-catenin staining patterns. There was an association between strong nuclear beta-catenin staining of stromal cells and epithelial Wnt5a expression (p<0.0015). These data suggest that stromal proliferation in benign phyllodes tumours relies on abnormalities in the Wnt pathway which result not from mutation, but from Wnt5a expression in the epithelium. In the progression to malignancy, the stromal proliferation appears to become independent of the Wnt pathway and, presumably, of the epithelial component of these tumours.     

肝癌组织中β—和p^120—连环蛋白的表达

目的 揭示连环蛋白与肝癌的发生发展的关系。方法 应用RT－PCT和免疫组织化学观察细胞黏附与信号转导分子β－和p^120－连环蛋白在正常肝组织、肝癌旁结节性肝硬化组织和肝癌组织中p^120ctn mRNA的蛋白质表达情况及其与β－连环蛋白的关系。结果 所有肝组织中均表达p^120 ctn mRNA同工蛋白1A和3A。2例正常肝组织中β－和p^120-连环蛋白分子表现为胞膜表达而胞质无表达;17例癌旁结节性肝硬化组织表现为胞膜和胞质均有表达,以胞质为主,且胞膜表达有所增强。17例HCC组织中表现为胞膜表达明显减弱或消失,而胞质表达则增强。多数细胞胞膜表达呈现不连续性。结论 肝组织中可检测到p^120ctn同工蛋白1A和3A mRNA。此外,正常肝组织中β－和p^120-连环蛋白分布在胞膜,对维持正常的细胞黏附和信号转导起重要作用;结节性肝硬化肝组织中此2种分子出现了分布变化,而肝癌细胞中此2种分子发生了明显的转位现象,提示肝癌细胞在一定程度上改变了细胞黏附分子的正常功能和其所介导的信号转导作用。     

上皮性钙粘附蛋白和β-连环素的表达与胆囊腺癌预后的关系

目的　探讨上皮性钙粘附蛋白 (E cad)及 β 连环素 (β cat)在胆囊腺癌中的表达及其与分化、转移、临床分期和预后的关系。方法　免疫组织化学法 (SP法 )和原位杂交法。结果　免疫组织化学法 :60例胆囊腺癌中E cad及 β cat的阳性率分别为 40 %和 45 % ,异常表达率分别为 58 3 %和 63 3 %。E cad和 β cat的异常表达率与胆囊腺癌的分化程度有相关性 (P <0 0 5) ,在有淋巴结转移病例中E cad及 β cat的异常表达率明显高于无转移病例 ,随着临床分期由Ⅰ期到Ⅳ期 ,E cad及 β cat异常表达率明显增高 (P <0 0 5)。E cad和 β cat异常表达病例的平均生存时间和 5年生存率明显低于正常表达病例。原位杂交法 :胆囊腺癌中E cad和 β catmRNA的阳性率分别为 60 %和 40 % ,与蛋白正常表达一致率分别为 78 8%和 82 4%。结论　检测 β cat或E cad和 β cat的共同表达是指导临床治疗及估计预后有意义的指标 ,可应用临床预后的综合评估     

β-catenin与wisp-1在结肠癌中的表达及意义

目的：探讨β-catenin与wisp-1 在原发性结肠癌中表达及临床意义。方法：分别用免疫组化Envision法和实时荧光定量PCR法检测β-catenin、wisp-1 蛋白和基因在53例结肠癌及53例配对正常结肠中的表达。分析两因子表达与临床病理的关系。结果：β-catenin、wisp-1蛋白在结肠癌的异常表达率均高于正常结肠中异常表达率（P〈0.05）。结肠癌中β-catenin蛋白异常表达与淋巴结转移、Duke分期和部位有关（P〈0.05）。wisp-1蛋白异常表达与淋巴结转移、Duke分期有关。β-catenin基因在结肠癌中平均表达是其在正常结肠中的3.237倍（P〈0.05），其异常表达与肿瘤部位及淋巴结转移有关（P〈0.05）。wisp-1基因在结肠癌中平均表达是其在正常结肠中的2.908倍（P〈0.05），其异常表达与肿瘤类型有关（P〈0.05）。结论：β-catenin与wisp-1异常表达特点提示两者与结肠癌的发生发展有密切关系。