c-Cbl、Cbl-b和EGFR在胃癌组织中的表达及其临床意义

Expressions of c-Cbl,Cbl-b,and epidermal growth factor receptor in gastric carcinoma and their clinical significance

背景与目的:c-Cbl和Cbl-b是CBL(the Casitas B-cell lymphoma)家族的两个重要成员,具有连接体功能及E3泛素连接酶功能,在表皮生长因子受体(epidermal growth factor receptor,EGFR)下调过程中发挥重要作用。本研究旨在探讨c-Cbl、Cbl-b和EGFR在胃癌组织中的表达及其临床意义。方法:将124例胃癌术后标本和16例癌旁正常胃组织制作成组织芯片,应用免疫组化方法检测c-Cbl、Cbl-b和EGFR的表达情况,并分析其与临床及病理因素的关系。结果:124例胃癌中c-Cbl、Cbl-b和EGFR的阳性率分别为71.0%、82.3%和56.5%,均显著高于癌旁正常胃组织(分别为18.0%、25.0%和12.5%,均P<0.01)。c-Cbl表达与浸润深度及病理分期呈正相关(r=0.219,P=0.015和r=0.266,P=0.003);Cbl-b表达与淋巴结转移及病理分期呈正相关(r=0.190,P=0.034和r=0.298,P=0.001);EGFR表达与浸润深度及病理分期呈正相关(r=0.286,P=0.001和r=0.362,P=0.000)。c-Cbl、Cbl-b与EGFR表达强度均呈正相关(r=0.241,P=0.007和r=0.183,P=0.042)。27例胃癌标本同时强阳性表达c-Cbl、Cbl-b和EGFR,多为分化程度差、肿瘤组织浸润程度深、淋巴结转移数目多及分期晚的病例。结论:c-Cbl、Cbl-b和EGFR的高表达与胃癌的侵袭和发展有关,c-Cbl和Cbl-b有可能成为胃癌新的分子标志物。

Background and Objective：c-Cbl and Cbl-b are two major members of the Casitas B-lineage lymphoma （Cbl） family,which play important roles in down-regulation of epidermal growth factor receptor （EGFR） by acting as E3 ubiquitin ligases and multi-adaptor proteins.This study was to investigate the expressions of c-Cbl,Cbl-b,and EGFR in gastric carcinoma and their clinical significance.Methods：The expressions of c-Cbl,Cbl-b,and EGFR were detected by immunohistochemistry using tissue microarrays consisting of 124 specimens of gastric carcinoma and 16 specimens of normal gastric mucosa.The relationship between the expressions of c-Cbl,Cbl-b,and EGFR and clinicopathologic factors of gastric carcinoma were analyzed statistically.Results：The positive rates of c-Cbl,Cbl-b,and EGFR were higher in the gastric carcinoma group than in the normal group （71.0% vs.18.0%,P〈0.01 82.3% vs.25.0%,P〈0.01 56.5% vs.12.5%,P〈0.01,respectively）.The expression of c-Cbl was positively correlated with depth o...更多f invasion （r=0.219,P=0.015） and TNM staging （r=0.266,P=0.003）.The expression of Cbl-b was positively correlated with lymph node metastasis （r=0.190,P=0.034） and TNM staging （r=0.298,P=0.001）.The expression of EGFR was positively correlated with depth of invasion （r=0.286,P=0.001） and TNM staging （r= 0.362,P=0.000）.The expression of c-Cbl or Cbl-b was positively correlated with EGFR （r=0.241,P=0.007 r=0.183,P=0.042,respectively）.Synchronously strong-positive expressions of c-Cbl,Cbl-b,and EGFR were observed in 27 specimens of gastric carcinoma,most of which were at advanced stage.Conclusion：The overexpressions of c-Cbl,Cbl-b,and EGFR are closely related to the invasion and progression of gastric carcinoma.c-Cbl and Cbl-b may serve as novel molecular markers for gastric carcinoma.