CDX2蛋白在肠上皮化生、胃癌组织中的表达及其意义

Expression and Significance of CDX2 Protein in Intestinal Metaplasia and Gastric Carcinoma

目的探讨尾侧型同源转录因子2(caudal type homeobox transcription factor 2,CDX2)在胃黏膜肠上皮化生、胃癌组织中的表达及其意义。方法采用CDX2单克隆抗体进行免疫组织化学染色,检测CDX2在肠化生、胃癌组织中的表达,同时检测Ki-67在胃癌组织中的表达,以确定癌细胞扩增率。结果CDX2在正常胃黏膜组织中无表达,在肠化生组织中阳性表达率为90.0%(18/20),在胃癌组织中阳性表达率为59.1%(29/49),两者有显著性差异(P=0.013)。按Laurén分型,肠型胃癌中CDX2蛋白阳性表达率高于弥漫型胃癌,并有非常显著性差异(73.5%:26.7%,P=0.002)。CDX2蛋白标记指数与Ki-67标记指数呈高度负相关(γs=-0.448,P=0.001),提示高CDX2标记指数胃癌细胞扩增率较低。此外,CDX2标记指数与肿瘤的TNM分期呈高度正相关(γs=-0.482,P<0.001)、与淋巴结转移呈负相关(γs=-0.382,P=0.012);与细胞分化程度呈高度正相关(γs=0.591,P<0.001)。肠型胃癌组织中CDX2表达亦呈现类似结果。结论CDX2的异常表达在胃黏膜肠上皮化生和胃癌,特别是肠型胃癌的发生中起着重要作用;高CDX2标记指数胃癌其侵袭性低,细胞分化程度高,淋巴结转移数量少,因而检测其表达强度有助于判断胃癌恶性程度及胃癌患者的预后。

Objective To investigate the expression of CDX2 in the gastric carcinoma（GC） and gastric intestinalmetaplasia （IM） and its significance. Methods By immunohistochemistry, CDX2 expression were tested in surgically dissected GC tissues from 49 patients, normal gastric mucosa tissues from 29 patients and gastric IM tissues from 20 patients. Tumor cell proliferation rate in GCs were evaluated by the detection of Ki-67 expression. Results CDX2 was not expressed in the normal gastric mucosa. The positive expression rate of CDX2 was 90.0% （18/20） in IM and 59.1% （29/49） in GC,showing a significant difference between the two groups（P = 0. 013）. CDX2 expression was also markedly different between intestinal-type GC and diffuse-type GC（73.5% vs. 26.7 %,P = 0. 002）. A negative association was observed between the index for CDX2 and Ki-67 immunostaining （γs = -0. 448, P = 0. 001）,indicating a low cell proliferation rate in GC with high CDX2 index. The expression of CDX2 was positively correlated with TNM stage（Ts =- - 0. 482, P 〈0. 001）and tumor differentiation（γs = 0. 591, P 〈 0. 001）, but negatively correlated with lymph node metastasis（γs= -0. 382,P = 0. 012）. The similar results were observed among the intestinal-type GC cases. Conclusion Abnormal expression of CDX2 plays an important role in the development of IM and GC, especially in intestinal-type GC. GCs with high CDX2 index have low invasion,high differentiation and fewer lymph node metastasis. Detection of CDX2 expression in gastric cancer tissues can be useful in the determination of malignancy and prognosis.