【作者】 刘仕琪；

【导师】 牛建华；

【作者基本信息】 石河子大学 ， 外科学， 2008， 硕士

【摘要】 目的: CDX-2与LI-cadherin在胃癌与癌前病变中的表达情况以及在发生癌变的胃黏膜上皮中的表达和分布至今仍不清楚,通过研究胃癌组织、癌旁组织、正常组胃黏膜组织、胃肠道间质瘤、慢性胃炎及肠化生胃黏膜组织中CDX-2与LI-cadherin的表达水平和分布情况,以及二者的表达阳性率与不同性别胃癌患者中表达的差异、与不同类型胃癌、细胞的分化程度、淋巴结转移程度、胃癌的浸润深度、胃癌的Laurien分期和临床分期的关系,研究二者在胃癌和癌前病变组织中的关系,探索胃黏膜癌前病变及癌变发生的分子机制。方法:分别应用即用型鼠单克隆抗体(CDX2-88)和羊多克隆抗体(C-17,sc-6987)利用S-P免疫组化检测246例不同胃组织(包括正常胃黏膜30例、慢性浅表性胃炎30例、慢性萎缩性胃炎42例、肠化生胃黏膜58例、胃腺癌46例、癌旁组织30例、胃间质瘤10例) CDX-2与LI-cadherin蛋白的表达情况。结果:CDX-2基因蛋白在正常胃黏膜及慢性胃炎中不表达;在肠化生组织中阳性表达率为91.4%(53/58);在胃癌组织中阳性表达率为80.4%(37/46),按Laurien分型,肠型胃癌中CDX-2蛋白阳性表达率高于弥漫型胃癌,并有显著性差异(P<0.050) ;CDX-2与细胞分化程度呈高度正相关(P<0.005),但与性别、年龄、浸润深度、胃癌分期及淋巴结转移无关。CDX-2在癌旁组织及胃间质瘤中无表达。LI-cadherin基因蛋白在正常胃黏膜及慢性胃炎中不表达;在肠化生组织中阳性表达率为83%(48/58);在胃腺癌组织中阳性表达率为65%(30/46),按Laurien分型,肠型胃癌中LI-cadherin蛋白阳性表达率(78%)高于弥漫型胃癌(35%),差异有统计学意义(P<0.050) ;LI-cadherin与淋巴结转移及临床分期明显正相关(P<0.010),在癌旁组织及胃间质瘤中无表达。CDX-2与LI-cadherin的过度表达紧密相关,而且CDX-2与LI-cadherin在肠化生胃黏膜中表现出很强的伴随关系。结论: CDX-2的异常表达可能与胃癌的早期发生有关,且可能是一种抑癌基因,CDX-2高表达胃癌其侵袭性低,细胞分化程度高,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。LI-cadherin的异常表达与肠化生及胃腺癌的发生有关, LI-cadherin高表达者淋巴结转移率高,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。CDX-2和LI-cadherine均是肠特异性标记物,而且二者在正常生理情况下均表达于小肠和结肠黏膜。本项研究表明,在胃黏膜肠化生和胃腺癌中CDX-2调节LI-cadherine的表达水平,后者被前者所诱导,尤其是在癌组织发生的初期,二者可能扮重要促癌作用。癌细胞局部侵犯或发生远处转移常常是导致临床治疗失败的主要原因,因此研究胃癌发病的分子机制和生物学行为对于寻找新的抗转移措施是非常关键的。更多还原

【Abstract】 Objective: CDX-2 and LI-cadherin in gastric cancer and precancerous lesions of the situation and in case of gastric cancer in epithelial expression and distribution are still unclear, through research the CDX-2 and LI-cadherin expression levels and distribution in gastric cancer, adjacent, normal gastric mucosa, Gastrointestinal stromal tumors, chronic gastritis and gastric intestinal metaplasia, and both the expression of different gender and the positive rate of gastric cancer patients in the expression of differences, and different Types of cancer, cell differentiation, metastasis of the depth of invasion of gastric cancer, gastric cancer Laurien stage and the relationship between the clinical stage, to studies the molecular mechanism of gastric cancer about the two factors in gastric cancer and precancerous lesions in the relationship between the exploration and gastric precancerous lesions.Methods: In this study we examined the expression of caudal-related homeo box transcription factor 2(CDX-2) with monoclonal antibody(CDX2-88)and LI-cadherin with Goat polyclonal antibody(C-17,sc-6987) using SP immunohistochemical detection of 246 cases of various stomach.Including two hundred and forty six specimens were collected,including normal epithelia(n=30), chronic superficial gastritis (n=30), chronic atrophic gastritis(n=42) , intestinal metaplasia (n=58),gastric adenocarcinoma(n=46), nearing cancer(n=30), gastric stromal tumor(n=10).The expression of CDX-2 was detected in alI the tissues by immunohischemistry.Results: The expression of CDX-2 in normaI epithelia and chronic gastritis are all negative , the positive rates of CDX-2 expresion in intestinal metaplasia and gastric adenocarcinoma are 91.4% and 80.4%,classification with Laurien, the positive rates of CDX-2 expresion in intestinal type and well-differentiated were higher than those in the diffuse type poorly differentiated (P<0.005).The expression of CDX-2 was independence of sex,age,depth of invasion, staging and lymph node metastasis. The nearing cancer and gastric stromal tumor exhibited negative CDX-2 expression.The expression of LI-cadherin in normaI epithelia and chronic gastritis are all negative , the positive rates of LI-cadherin expresion in intestinal metaplasia and gastric adenocarcinoma are 83 % (48/58) and 65 %(30/46),classification with Laurien, the positive rates of LI-cadherin expresion in intestinal type were higher(78%) than those in the diffuse type (35%) (P<0.050).LI-cadherin is positive correlation with lymph node metastasis and staging. The nearing cancer and gastric stromal tumor exhibited negative LI-cadherin expression. LI-cadherin expression closely related to the excessive of CDX-2 in gastric adenocarcinoma, forthemore, CDX-2 and LI-cadherin in the intestinal metaplasia gastric shown a strong relationship.Conclusion: The abnormal expression of CDX-2 was correlated with early stag of GC, maybe it plays an anti-oncogene role in the development of gastric carcinoma. GCs with high CDX-2 index have low invasion,high differentiation ,and Detection of CDX-2 expression in gastric cancer tisues can be useful in the determination of malignancy and prognosis.The abnormal expression of LI-cadherin was correlated with intestinal metaplasia and gastric adenocarcinoma. GCs with high LI-cadherin index have more lymph node metastasis, The Detection of LI-cadherin expression in gastric cancer tissues can be useful in the determination of malignancy and prognosis.CDX-2 and LI-intestinal cadherine are specific markers, and two in the normal physiological circumstances expression in the small intestine and colon mucosa. This study shows that in gastric intestinal metaplasia and gastric adenocarcinoma in the CDX-2 LI-cadherine regulating the expression level, the latter being induced by the former, especially in the early stages of cancer occur, and they may be playing an important role in tumor promoter . Local cancer violations or distant metastasis often lead to treatment failure of the main reasons, the incidence of gastric cancer on the molecular mechanism of the biological behavior and the search for new anti-transfer measures is crucial.更多还原