【作者】 杜芸； 左连富； 王小玲；

【Author】 Du Yun Zuo Lian-Fu Wang Xiao-Ling Department of pathology, The fourth hospital of Hebei medical university & Hebei provincial tumor hospital, Shijiazhuang, 050011, China

【机构】 河北医科大学第四医院暨河北省肿瘤医院病理科；

【摘要】 目的:跨膜信号转导对肿瘤的侵袭转移起重要作用,近年来大量实验表明,肿瘤细胞转移的各个阶段,如与细胞外基质的相互作用、肿瘤细胞的运动、黏附侵袭及血管生成等都与肿瘤细胞的跨膜信息传递机制密切相关。c—Src 是非受体酪氨酸激酶-Srcc—Src是非受体酪氨酸激酶-Src 家族的成员之一,介导众多细胞信号转导通路。我们以c— Src为中心,同时检测反映细胞增殖状态的mcm2、与脉管生成有关的Nos-2和VEGF、以及与肿瘤的侵袭迁移有关的 E—cadherin在食管鳞癌上的表达,探讨c-Src与这些蛋白的相关性,以及对食管癌的分化、分期及生存率的影响。方法: 通过免疫组化及原位杂交的方法检测食管鳞癌上c-Src及其相关因子的表达。结果:c—Src在134例食管鳞癌的阳性表达率为98．5％,c—Src在食管鳞癌上的表达强弱与食管癌的分化、分期密切相关(P=0．001,0．041),c—Src与MCM2 呈明显正相关(rs=0．43184,P=0．0001);c—Src与VEGF 呈正相关(rs=0．21795,P=0．0114);c-Src与NOS2呈正相关(rs=0．17149,P=0．0476);c-Src与E—cadherin无明显相关性(rs=-0．156,P=0．072)。COX回归模型显示:临床分期、C-Src、MCM2和NOS2为独立的预后因素。结论: c-Src表达强弱与食管鳞状细胞癌的分化和临床分期密切相关,分化越低、临床分期越晚,其过表达越明显;c—Src、 MCM2、临床分期和NOS2可作为食管鳞状细胞癌的独立预后指标;通过检测c—Src与mcm2、E—cadherin、NOS2和 VEGF的相关性,进一步证实了c—Src可通过多种途径,如增强肿瘤细胞的增殖,增加肿瘤细胞的迁移潜力,降低黏附,促进血管生成等促进食管鳞状细胞癌的侵袭和转移。更多还原

【Abstract】 Objective: Signal transduction plays a critical role in invasion and metastasis of tumour. Many studies have demonstrated that every stage of cancer metastasis, including interaction with matrix, cell motility, adhesion and angiogenesis is associated with signal transduction. c-Src is one of non-receptor protein tyrosine kinases, mediating a variety of signal transduction pathways. Using im-munohistochemistry and in situ hybridization(ISH), we examine the expressions of c-Src and its related gene proteins, including MCM2, NOS2, E-Cadherin, VEGF to study their relationships and influences on the differentiation, stage and survival of ESCC. Methods : Using immunohistochemistry and in situ hybridization (ISH). Results: 134 ESCC patients was 98.5%, the expression level was significantly higher in poorly-differentiated ESCC than in well-differentiated ESCC(P=0.001), Overexpression of c-Src was related to clinical stage, the expression level was higher in Stage III than in Stage I (P= 0.041), Positive correlation was found between c-Src and MCM2 ( r=0.43184,P=0.0001), c-Src and VEGF ( r= 0.21795,P=0.0114), c-Src and NOS2( rs=0.17149,P= 0.0476). C-Src was not correlated with E-cadherin (r= -0.156,P=0.072). Conclusion: We detected c-Src mRNA and protein levels in ESCC by ISH and immunohistochemistry, analyzed its correlation with MCM2, E-Cadherin, NOS2 and VEGF .studied its role in tumour invasion and metastasis. No report like this has been found in our country. The result showed that c-Src was closely related to the differentiation and stage of ESCC. c-Src, MCM2, NOS2 and tumour stage were independent prognostic factors. By studying the correlationship between c-Src and its related factors(MCM2, NOS2, VEGF, E-cadherin), we demonstrated that c-Src could promote invasion and metastasis of tumors by a varerty of pathways, including stimulating proliferation, motility and angiogenesis, inducing adhesion of tumour cells.更多还原