E-钙粘素在结直肠癌中的表达及其与淋巴结微转移的关系
3 讨论
E-Cadherin又称细胞-细胞粘附分子,广泛分布于各类上皮细胞间介导同型细胞间连接的、具有钙依赖性的粘附分子,其在胚胎发育、形态发生、上皮极性和完整性等方面起到重要作用[5]。其表达程度及功能活性状态直接影响细胞的脱落和再粘着,对维持组织结构的完整性、极性及细胞分化等起重要作用[6]。其表达下降时细胞的粘附作用减弱,使肿瘤细胞发生浸润和转移[7]。
本研究表明,E-Cadherin在高分化型结直肠癌的表达明显高于未分化型的结直肠癌,提示E-Cadherin与肿瘤的分化有关,可作为分子标记物来鉴别肿瘤的恶性程度。本组资料显示E-Cadherin的异常表达与结直肠癌的病理组织类型无明显相关性,主要考虑与各型腺癌结构的分化和异型程度不一致造成,例如管状腺癌就包括高、中、低分化三种类型。
多数学者认为E-Cadherin是肿瘤浸润抑制基因[8,9]。文献报道,结直肠癌E-Cadherin表达异常与肿瘤分化及浸润深度密切相关,与本研究发现一致。可见E-Cadherin可以作为大肠癌的标志物,协助判断大肠癌的预后。
研究证明,淋巴结微转移与患者预后直接相关。CK20是一种独特的I型细胞角蛋白,为具有严格的上皮特异性的癌细胞标志物,可稳定地存在于几乎所有的胃肠道癌及其转移癌中,正常血液及淋巴结的固有成分如淋巴细胞、内皮细胞一般不表达,是检测直肠癌微转移较特异的指标[10,11]。我们应用RT-PCR检测CK-20阳性率为(55.8%),而传统病理切片诊断为淋巴结转移的阳性率为(45.5%),两组间有显著性差异(P<0.001)。
11例检出淋巴结微转移患者癌组织中6例(54.5%)E-Cadherin表达阴性,而15例未检出微转移癌组织中仅有1例(6.67%)表达阴性,两者差异有统计学意义(P=0.041)。本研究提示E-Cadherin的表达减弱或消失参与了结直肠癌淋巴结微转移的发生。
参考文献
[1] Maurer CA,Graber Hu,Friess H,et al.Reduced expression of the metastasis suppressor gene KAI1 in advanced colon cancer and its metastases.Surgery,1999,126(5):869-880.
[2] Oberg A,Stenling R,Tavelin B,et al,Are lymph node micrometastasis of any clinical significance in Dukes stages A and B colorectal cancer.Dis Colon Rectum,1998,41(10):1244-1249.
[3] Spiliotis J,Datsis A.The surgical approach to locally recurrent rectal cancer.Tech coloproctol,2004,8(Suppl 1):s33-35.
[4] Yamaguchi K,Takagi Y,Aoki S,et al.Significant detection of circulating cancer cells in the blood by reverse transcriptase-polymerase chain reaction during colorectal cancer resection.Ann surg,2000,232(1):58-65.
[5] Takeichi M.Cadherin Cell Adhesion Receptors as a Morphogentic Regulator.Science,1991,251:1451.
[6] Mc Neill H,Ozawa M,Kemler R,et al.Novel function of the cell adhersion molecule uvomrulin as a inducer of cell surface polarity.Cell,1990,62:309.
[7] Aoki R,Yasuda M,Torisu R,et al.Relationship between lymph node metastasis and E-Cadherin expression in submucosal invasive gastric carcinomas with gastric-phenotype.J Med Invest,2007,54(1-2):159-167.
[8] Vleminckx K,Vakaet L,Mareel M,et al.Genetic manipulation of E-Cadherin expression by epithelial tumor cells reveals an invasion suppressor role.Cell,1991,66(1):107-119.
[9] Nagafuchi A,Takeichi M.Cell binding function of E-Cadherin is regulated by the cytoplasmic domain.EMBOJ,1988,7(2):3679-3684.
[10] Cytokeration 20 in human carcinomas.A new histodiagnostic marker detected by monoclonal antibodies.Am J Pathol,1992,140:427-47.
[11] 冯国丽,曾庆良,宋璇,等.CD4+、CD8+和NK在结直肠癌中的表达及其与淋巴结微转移的关系.中华实验外科杂志,2009,26(2):159-161.
