大肠癌原发灶和肝转移灶DCC基因存在状态的研究

Comparative study of DCC gene status between primary and liver metastatic lesions of large intestinal cancer

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 understand DCC gene status between primary and liver metastatic lesions of large intestinal cancer. Methods: Immunohistochemistry and PCR- SSCP were applicated to detect DCC protem expression and DCC cDNA sequence muta-tion in 136 cases of large intestinal cancer recurrence after operation and 30 cases of primary and liver metastatic large intestinal can-cer. Results:The expression of DCC gene was decreased the cancer, which was related to the recurrence. Patients with liver metasta-sis were appeared negative DCC protein, 92.2% DCC profein negative cases had lost reoperation opportunity and took place recur-rence within one year after reoperation 71.4% DCC positive cases could reoperate with longer survival stage after operation. SSCP analysis showed that mutation rate of DCC cDNA sequence was 40% in primary cancer and 48.8% in liver metastatic cancer. Con-clusions; The inactivation of DCC gene is an important factor which influences prognosis of large intestinal cancer. The mechanism of DCC gene inactivation is mainly DCC sequence mutation.