β-连接素在胃癌的表达及其与患者生存的关系

Relationship between Abnormal Expr ession of β-catenin in Gastric Carcinoma and Survival

背景与目的:细胞粘附功能下降是恶性肿瘤发展的关键因素。作为粘附分子的E-钙粘蛋白在维持正常组织结构方面具有非常重要的作用,但其功能的发挥,需要配体-连接素(α-、β-连接素等)的调节。为探讨β-连接素在胃癌发病机制中的作用,我们研究β-连接素在胃癌的表达情况,并分析其与临床病理特征及生存期的关系。方法:采用免疫组织化学法检测148例胃癌石蜡标本β-连接素和E-钙粘蛋白的表达水平。结果:胃癌组织β-连接素和E-钙粘蛋白的异常表达率分别为43.2%和44.6%;胃癌β-连接素和E-钙粘蛋白其中一种或二种表达异常者达63%。β-连接素和E-钙粘蛋白在低分化癌的异常表达率显著高于高分化癌(均P<0.005)。β-连接素表达异常与胃癌浸润深度密切相关(P<0.025);淋巴结转移阳性(45/84,53.6%)及发生远处转移(21/31,67.7%)的β-连接素异常表达率显著高于淋巴结转移阴性(19/64,29.7%)(P<0.005)及无远处转移者(43/117,36.8%)(P<0.005)。β-连接素正常表达比异常表达具有生存优势(P<0.005),且独立于浸润深度、淋巴结转移及分化程度。结论:胃癌广泛存在E-钙粘蛋白复合体表达异常;β-连接素异常表达是对胃癌生存期具有预测价值的重要指标。

Background &Objective:Altered cell adhesion has a critica l role in the development of epitheli al cancers.E-cadherin act on the maint enance of cell-cell adhesion and its function was thought to be regulated by associated cytoplasmic proteins,such asα-catenin andβ-catenin .This study was designed to examine the expression ofβ-catenin in gastric carcinoma and to determine t he relationship between tumor chara cteristics and survival.Methods :Immunohistochemical staining ofβ-catenin and E-cadherin was perform ed in 148patients with gastric carcinoma.Results:Abnormal expression ofβ-catenin and E-cadherin was demonstrated in 43.2%and 44.6%of tumors respectively.Up to63%of tumors stained abnormally for one or two components of the cadherin-catenin complex(β-catenin,E-cadherin).Abnormalβ-catenin and E-cadherin staining oc curred more frequently in poor diffe rentiated tumor than in good differe ntiated tumors(P<0.005,respectively).There was a significant correlation between abnormalβ-catenin expression and depth of invasion(P<0.025).Moreover,abnormalβ-catenin expression was more frequent in tumors with positive lymph node metastasis 537(45/84,53.6%)and distance metastasis(21/31,67.7%)than in tumors without lymph node metastasis(19/64,29.7%)(P<0.005)and distance metastasis(43/117,36.8%)(P<0.005).A survival advantage was noted in tu mors retaining normal membranous expression ofβ-catenin,independent of type,grad e,or stage(P<0.005).Conclusions :Abnormal expression of the E-cadherin-catenin complex occurs frequent ly in gatric carcinoma.The close correlation with poor survival suggests that abnorma lβ-catenin may be a useful prognostic marker.