遗传性非息肉病性大肠癌中hMSH2，hMLH1，TβRⅡ，MMP-7及TIMP-2的表达和其特殊生物学行为间的关系  

Expression of hMSH2,hMLH1,transforming growth factor β receptor type Ⅱ,matrix metalloproteinase-7,tissue inhibitor of metalloproteinase-2 and their correlations with the biological behaviors of hereditary nonpolyposis colorectal cancer

作　　者：顾国利[1] 魏学明[1] 王石林[1] 任力[2] 胡益云[2] 李德昌[2] 

机构地区：[1]中国人民解放军空军总医院普通外科,北京市100036 [2]中国人民解放军空军总医院病理科,北京市100036

出　　处：《世界华人消化杂志》2007年第15期1738-1744,共7页World Chinese Journal of Digestology

摘　　要：目的:探讨遗传性非息肉病性大肠癌(HNPCC)中错配修复基因hMSH2、hMLH1、转化生长因子βⅡ型受体(TβRⅡ)、基质金属蛋白酶-7(MMP-7)、组织抑制因子-2(TIMP-2)表达的相互关系及其与HNPCC特殊生物学行为的关系.方法:应用免疫组织化学染色法检测HNPCC和散发性大肠癌(SCRC)肿瘤组织石蜡标本各30例、正常大肠黏膜石蜡标本8例.观察其hMSH2,hMLH1,TβRⅡ,MMP-7,TIMP-2的表达,并结合临床病理资料综合分析.结果:在HNPCC和SCRC中,hMSH2,hMLH1,TβRⅡ,MMP-7,TIMP-2均与患者的性别、肿瘤大小和部位无关;而与肿瘤的侵犯深度和是否转移密切相关,阳性表达率差异显著(P<0.05,HNPCC vs sporadic CRC).在HNPCC中,hMSH2和hMLH1(r=0.835,P= 0.000),TβRⅡ与hMSH2(r=0.592,P=0.001),hMLH1(r=0.472,P=0.009)和MMP-7(r= 0.735,P=0.000)表达均呈明显正相关;而TIMP-2与TβRⅡ(r=-0.582,P=0.001),MMP-7(r=-0.421,P=0.008)表达呈明显负相关.结论:由于hMSH2,hMLH1突变引起TβRⅡ的失活而诱导的MMP表达减弱和TIMP的下调可能是HNPCC特殊生物学行为的一个原因.AIM： To investigate the correlation of hMSH2, hMLH1, transforming growth factor β receptor type Ⅱ （TβRⅡ）, matrix metalloproteinase-7 （MMP-7） and tissue inhibitor of metalloproteinase-2 （TIMP-2） expression with the biological behaviours of human hereditary nonpolyposis colorectal cancer （HNPCC）. METHODS： Immunohistochemical staining was used to detect the expression of hMSH2, hMLH1, TβRⅡ, MMP-7 and TIMP-2 protein in 30 cases of sporadic colorectal cancer （SCRC）, 30 cases of HNPCC and 8 cases of normal colorectal mucosa, and their corresponding clinical datas were studied retrospectively. RESULTS： The positive rates of hMSH2, hMLH1, TβRⅡ, MMP-7 and TIMP-2 expression were significantly related to the depth of invasion and lymph node metastasis, but not to the sex of patients and the size or position of tumors. The positive rates of hMSH2, hMLH1, TβRⅡ, MMP-7 and TIMP-2 expression were remarkably different between SCRC and HNPCC （P 〈 0.05）. The expression of hMSH2 had a positive correlation with hMLH1 （r = 0.835, P 〈 0.01）; The expression of TβRⅡ had positive correlations with hMSH2 （r = 0.592, P 〈 0.01）, hMLH1 （r = 0.472, P 〈 0.01） and MMP-7 （r = 0.735, P 〈 0.01）, while the expression of MMP-7 had nega- tive correlations with TβRⅡ （r = -0.582, P 〈 0.01）, TIMP-2 （r = -0.421, P 〈 0.01） in HNPCC. CONCLUSION： The mutations of hMSH2 and hMLH1 beget the inactivation of TβRⅡ in HNPCC, which induces down-regulated expression of MMP-7 and up-regulated expression of TIMP-2. This might be one reason for the special biological behaviours of HNPCC.

关 键 词：遗传性非息肉病性大肠癌 散发性大肠癌 错配修复基因 转化生长因子βⅡ型受体 基质金属蛋白酶-7 基质金属蛋白酶组织抑制因子-2 免疫组织化学 

分 类 号：R735.34[医药卫生—肿瘤]