【作者】 郭闻渊；

【导师】 陈学云；

【作者基本信息】 第二军医大学 ， 外科学（普外）， 2001， 硕士

【摘要】 背景：DPC₄基因是一个抑癌基因，K-ras基因是癌基因，两者均具有胰腺癌特异性，它们的基因产物分别为Smad₄和P^21ras蛋白。目的：分析抑癌蛋白Smad₄和癌蛋白P^21ras在胰腺癌和壶腹周围癌组织中的表达及其与胰腺癌的临床和病理特征的关系，了解两种蛋白对胰腺癌与壶腹周围癌鉴别诊断的意义。方法：采用Smad₄和P^21ras的单克隆抗体和免疫组织化学EnVision方法分别检测石蜡包埋的22例胰腺癌、15例壶腹周围癌、9例胰腺癌远处淋巴结转移组织、18例良性胰腺病变组织和3例正常胰腺组织共67例标本中的Smad₄蛋白失活和P^21ras蛋白表达情况，所有被检标本均经病理诊断证实。结果：胰腺癌中，Smad₄蛋白失活率为50.00％（11/22）；壶腹周围癌中的失活率为13.33％（2/15）；胰腺癌远处淋巴结转移组织中失活率为44.44％（4/9）；胰腺良性病变中为16.67％（3/18），其中慢性胰腺炎为23.08％（3/13），胰腺囊肿和胰腺囊腺瘤未发现该蛋白失活；正常胰腺中无该蛋白失活。P^21ras蛋白在胰腺癌中的表达率为77.27％（17/22）；在壶腹周围癌中表达率为26.67％（4/15）；胰腺癌远处淋巴结转移组织中的表达率为44.44％（4/9）；良性胰腺病变中的表达率为38.89％（7/18），其中慢性胰腺炎为38.46％（5/13），胰腺囊腺瘤为100.00％（2/2），胰腺囊肿未发现该蛋白表达；正常胰腺中未发现该蛋白表达。胰腺癌与壶腹周围癌、胰腺良性病变间Smad₄蛋白的失活率及P^21ras蛋白表达率有显著差异（p＜0.05）。胰腺癌中Smad₄蛋白的失活率和P^21ras蛋白表达率与患者年龄、性别、症状、肿块大小、肿瘤部位、病理分级、临床分期和淋巴结转移无明显相关（p＞0.05）。各病变Smad₄蛋白失活率与P^21ras蛋白表达率间无相关关系（p＞O.05）。结论：用免疫组织化学方法检测Smad₄和P^21ras蛋白已成为了解胰腺癌中DPC₄和K-ras基因改变的非常敏感、特异的方法。两种蛋白的检测有助于胰腺癌与壶腹周围癌、良性胰腺病变的鉴别诊断。在K-ras基因突变这一胰腺癌发生的早期事件之后，DPC₄基因在促进胰腺癌进一步发展中起着重要作用。更多还原

【Abstract】 Background: DPC4 gene is an anti-oncogene, K-ras is an oncogene, both of them are specific markers to pancreatic carcinoma, and their products are2 ras protein Smad4 and P Objective: To investigate the expression of anti-oncogene product Smad4 and oncogene product P2lras in pancreatic carcinoma and periampullar carcinoma, and the relationship of them to the clinic pathological characteratics; to elucidate the role of the two proteins expression on the differential diagnosis of pancreatic carcinoma and periampullar carcinoma. Methods: 67 paraffin-embedded and pathologically proved specimens including pancreatic carcinoma (n=22), periampullar carcinoma (n=1 5), lymph node with pancreatic carcinoma metastasis (n9), benign disease of pancreas (n=1 8) and normal pancreas (m=3) were immunohistochemically stained with monoclonal primary antibodies of Smad4 and p2lras respectively by using the EnVision system. Results: Loss of Smad4 was detected in II specimens of 22 pancreatic carcinomas (50.00%), 2 of 15 periampullar carcinomas (13.33%), 4 of 9 lymph nodes with pancreatic carcinoma metastasis (44.44%), 3 of 18 benign diseases of pancreas (16.67%), 3 of 13 chronic pancreatitis (23.08%) and none of 3 normal pancreata (0.00%). The positive2lras expression rate of P was 77.27% in pancreatic carcinomas (17/22), 26.67% in periampullar carcinomas (4/15), 44.44% in lymph nodes with pancreatic carcinoma metastasis (4/9), 3 8.89% in benign diseases of pancreas (7/18), 38.46% in chronic pancreatitis (5/13) and none in normal pancreata (0/3) respectively. The loss of Smad4 showed significant difference in pancreatic carcinoma and periampullar carcinoma as compared to benign disease of pancreas (p <0.05) , so did the positive expression 0fp2lraS (p <0.05) . The loss of Smad4 was not significant related to the age, sex, symptom, tumor size, tumor site, pathological degree, clinical stages and lymph node metastasis (p >0.05) ,. and neither was the expression of p2lras (p >0.05) . Loss of Smad4 was not related to the expression 0fp2lras in each disease (p >0.05) ,just as reported in other carcinomas. Conclusions: Immunohistochemical labeling for theSmad4 and P2lras has been shown to be an extremely sensitive and specific method fordetecting the DPC4 and K-ras alterations in pancreatic carcinoma. To detect DPC4 andK-ras gene expression could be helpful in the differential diagnosis amongpancreatic carcinoma, periampullar carcinoma and the benign diseases. The K-rasgene occurs early in the carcinogenesis of pancreatic carcinoma, and thereafter theloss of DPC# plays a very important role in the progress of pancreatic carcinoma.更多还原