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目的:了解DCC基因在大肠癌复发、转移过程中的变化及其与肝转移的关系.方法:采用免疫组化和多聚酶链反应一单链构象多态性分析(PCR-SSCP)对136例大肠癌术后复发患者和30例有肝转移的大肠癌原发灶及肝转移灶进行了DCC基因存在状态的研究.结果:大肠癌DCC基因蛋白多数呈阴性表达,且与局部复发关系密切,局部复发者DCC表达下降明显.肝转移者多数发生DCC表达失活,DCC蛋白阴性者92.9%(26/28)失去再手术的机会或虽勉强手术但不到1年内即复发,而DCC蛋白阳性者71.4%(5/7)可再手术且术后存活期较长.经SSCP分析,有肝转移的大肠癌原发灶DCC基因cDNA序列变异率为40%(14/35),皆为DCC蛋白阴性的患者,肝转移灶变异率为48.8%(17/35).结论:DCC基因失活可能是影响大肠癌预后的重要因素之一,肝转移者发生DCC表达失活的主要机制是发生了基因突变.
Objective: To investigate the changes of DCC gene during recurrence and metastasis of colorectal cancer and its relationship with hepatic metastasis. Methods: Immunohistochemistry and polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP) were used in 136 cases of large intestine The status of DCC gene was studied in patients with cancer recurrence and 30 cases of primary tumors and liver metastases with liver metastases. Results: The majority of DCC gene proteins were negatively expressed in colorectal cancer and were closely related to local recurrence. DCC expression was significantly decreased in relapsed individuals. DCC expression was inactivated in most cases of liver metastases. 92.9% (26/28) of DCC-negative patients lost the chance of reoperation or relapsed within less than 1 year despite aggressive surgery, whereas DCC protein positive patients 71.4% (5/7) were reoperative and survived longer. After SSCP analysis, the DCC gene mutation rate was 40% (14/35) in the primary tumors with hepatic metastases. Both were DCC proteins. In the negative patients, the hepatic metastasis mutation rate was 48.8% (17/35). Conclusion: DCC gene inactivation may be one of the important factors affecting the prognosis of colorectal cancer. The main mechanism of DCC inactivation in liver metastasis is the occurrence of Gene mutation.