【作者】 黄凯；

【导师】 许东坡； 叶建新；

【作者基本信息】 福建医科大学 ， 外科学， 2003， 硕士

【摘要】 目的： 探讨APC、β-catenin在散发性结直肠肿瘤发生、发展中的作用和临床意义。 方法： 用SP免疫组化方法检测55例散发性结直肠腺癌、33例结直肠腺瘤组织标本中APC、β-catenin基因蛋白产物的表达水平，并与临床参数相比较。 结果： (1) APC基因蛋白产物在结直肠腺癌组织中失表达率(76.4％)明显高于结直肠腺瘤(27.3％)和正常粘膜组织(13.3％)，差别有显著性(P＜0.05)。 (2) APC基因蛋白产物在结直肠绒毛状腺瘤(villous adenomas)中失表达率(100％)明显高于管状腺瘤(tubular adenomas)(11.8％)和混合型腺瘤(mixed adenomas)(25％)(P＜0.05)。 (3) 结直肠癌APC基因蛋白产物表达与患者的年龄、性别、肿瘤的大小、部位、大体类型、分化程度、Dukes分期以及淋巴结转移与否无关(P＞0.05。 (4) β-catenin在结直肠腺癌组织和腺瘤组织中细胞核阳性表达(45／55 81.8％、23／33 69.7％)明显高于正常粘膜组织(0)(P＜0.05)。 (5) 低分化腺癌β-catenin细胞核阳性表达率(13／13)明显高于中、高分化结直肠腺癌(19／23、13／19)(P＜0.05)；淋巴结阳性组β-catenin细胞核阳性表达率(25／27 92.6％)明显高于阴性组(20／28 71.4％)(P＜0.05)；Dukes C、D期(31／34 91.2％)明显高于Dukes A、B期结直肠腺癌(14／21 66.7％)(P＜0.05)。β-catenin细胞核阳性表达与结直肠腺癌的大小、部位、患者的年龄、性别无关。(6)结直肠腺瘤中APC与刀一catenin的表达无关;而结直肠腺癌中APc的表 达与户catenin的表达呈负相关关系。结论:(l)APc、厅一catenin参与了散发性结直肠肿瘤的发生发展过程;其基因蛋白产 物表达的异常(APC失表达、刀一catenin细胞核异位表达)是散发性结直肠 肿瘤的发生发展过程中的早期可见改变，且刀一catenin核聚集主要是由于 APC蛋白产物功能失活所致。(2)妙C的失表达可能与散发性结直肠腺瘤恶性转化易感性有关。(3)刀一catenin蛋白产物的细胞核异位表达与散发性结直肠腺癌细胞的转移和肿 瘤的去分化及其恶性行为有关。(4)检测结直肠肿瘤组织APC、刀一catenin基因蛋白产物的表达情况对病理学者 和临床医师判断其恶性潜能有重要参考价值，也为结直肠腺瘤的随访和内 镜检查时机提供了理论依据。更多还原

【Abstract】 ObjectiveTo explore the role of APC and β -catenin in the carcinogenesis and progression ofsporadic colorectal adenocarcinoma.MethodsImmunohistochemical methods were used to detect the expression of APC and β -catenin protein in 45 cases of normal colorectal mucosa, 33 cases of sporadic colorectal adenoma, 55 cases of sporadic colorectal carcinoma,and the results were correlated with clinicopathological tumor parameters. Results(1) The percentage of APC protein loss expression in colorectal adenocarcinomas (76.4%) was significantly greater than that in colorectal adenomas (27.3%) and normal colorectal mucosa tissues (13.3%)( P<0.05).(2) The negative rate of APC protein expression in colorectal villous adenomas was significantly greater than that in colorectal tubular adenomas and mixed adenomas.(3) There were no significant difference in the incidence of APC protein expression in sporadic colorectal adenocarcinoma among the different age ,sex groups and the different site ,size, histopathological type , lymph node involvement, differentiated degree, Dukes’ stage groups.(4) The percentages of β -catenin nuclear expression in the colorectaladenocarcinomas (88%) and adenomas (69.7%) were significantly greater than that in normal mucosa tissues (0%)(P<0.05).(5) The positive stain rate of β -catenin nuclear expression in moderate ,well differentiated colorectal adenocarcinomas (19/23 13/19 respectively) was less than that in poorly differentiated colorectal adenocarcinomas (13/13)( P<0.05).The percentage of β -catenin nuclear expression in lymphonodi metastases group (92.6%)was greater than that in non-lymphonodi metastases group (71.4%)( P<0.05).Thenuclear positive rate of β -catenin protein expression in the Dukes’ A B stage groupwas lower than that in Dukes’ C D stage group. There was no significant differences inthe incidence of !-catenin protein expression among different age ,sex groups anddifferent site, size of the colorectal adenocarcinomas groups.(6) There was an inverse correlation between APC and β -catenin protein expressionin colorectal adenocarcinomas and there was no correlation between loss of APC andnuclear accumulation of β -catenin in colorectal adenomas.Conclusion(1) APC and β -catenin protein plays an important role in carcinogenesis of sporadiccolorectal adenocarcinomas. Aberrant expressions(loss of APC expression ,nuclearaccumulation of β -catenin) of APC and β -catenin in sporadic colorectaladenocarcinomas are an early alteration. The major cause of β -catenin nuclearaccumulation in colorectal tumors is dysfunction of APC.(2)Loss of APC protein production expression may be associated with susceptibility of transformation from benign adenoma to adenocarcinoma in large bowel. (3)Abnormal nuclear expression of β -catenin in sporadic colorectal adenocarcinoma is associated with metastasis, de-differentiation and malignant behavior of tumors. (4)The detection of the expression of APC and β -catenin in colorectal carcinomas is valuable for evaluating the biological behavior of colorectal carcinomas and is beneficial to focal follow-up and repeat endoscopic control for diagnostic and clinical purposes.更多还原