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目的探讨胆囊癌中有关p16基因缺损、突变等异常状态以及不同病理类型及分化程度的胆囊癌与其转移和预后的关系。方法应用PCR、SSCP分析及DNA序列测定技术研究48例原发性恶性胆囊癌患者的手术病理标本的癌组织的p16基因外显子的异常情况,结合患者随访资料进行预后情况分析。结果(1)p16基因的缺损率与胆囊癌组织病理类型无关(P>0.05)。(2)p16基因在48例恶性胆囊癌的总缺损率为45.83%;p16基因缺损率与癌组织学分级密切相关,分化程度低的癌组织p16基因缺损检出率高(P<0.01)。(3)所有p16基因缺损的22例患者的转移率高(P<0.05),已发生转移的胆囊癌病例数中,其p16基因缺损率高达72.73%,而未发生转移的胆囊癌病例中,其p16基因缺损率为22.73%。(4)所有检出p16基因缺损的患者,3年生存率低(P<0.05)。结论p16抑癌基因的缺损可能参与胆囊癌的发生、发展过程,并且可能与其转移事件发生及其预后均密切相关,检测p16基因缺损率可作为判断胆囊癌预后的参考指标。
Objective To investigate the relationship between gallbladder carcinoma and the metastasis and prognosis of gallbladder carcinoma in relation to the abnormality of p16 gene, mutation and other pathological types and differentiation. Methods PCR, SSCP analysis and DNA sequencing were used to study the abnormalities of p16 exon in 48 cases of primary malignant gallbladder carcinoma. The prognosis of patients with pathological specimens were analyzed retrospectively. Results (1) The deletion rate of p16 gene was not related to the pathological type of gallbladder carcinoma (P> 0.05). (2) The total defect rate of p16 gene in 48 cases of malignant gallbladder cancer was 45.83%. The rate of p16 gene deletion was closely related to the histological grade of cancer. The rate of p16 gene deletion in cancerous tissues with low differentiation was high (P <0.01). (3) The rate of p16 gene deletion in all the 22 cases with p16 gene deletion was high (P <0.05). The number of cases with metastatic gallbladder carcinoma was 72.73%, but in cases without metastasis, The p16 gene deletion rate was 22.73%. (4) The 3-year survival rate was lower in all patients with p16 gene deletion (P <0.05). Conclusion The deletion of p16 gene may play an important role in the carcinogenesis and progression of gallbladder carcinomas, and may be related to the occurrence of metastasis and its prognosis. Detecting the rate of p16 gene deletion may be used as a reference index for prognosis of gallbladder carcinoma.