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目的 探讨肝细胞癌(HCC)8号染色体微卫星变异的特点及其与临床病理的相关性。方法采用MegaBACE 500型自动化DNA分析系统,对56例HCC中8号染色体上10个微卫星的杂合性缺失(LOH)、微卫星不稳定性(MSI)和等位基因失衡(AI)3种变异特征进行检测。结果 56 例HCC 在8 号染色体上10 个基因座发生LOH 的总频率为66.1%(37 /56),MSI 的频率为12.5%(7 /56),AI的频率为19.6%(11/56)。LOH以D8S261最高为53.5%(23/43),其次为D8S1721(52.5%)和D8S1771(52.5%)。D8S277基因座,血清HBsAg阳性患者的LOH频率显著高于HBsAg阴性者(P<0.01),D8S261、D8S298和D8S1733基因座,血清HBsAg阴性患者的LOH频率显著高于HBsAg阳性者(P<0.01);D8S298和D8S1771基因座,肿瘤直径>3cm的LOH率明显高于￣<3cm组(P<0.05和P<0.01);在D8S1721基因座,无包膜或包膜不完整的肿瘤的LOH显著高于包膜完整的肿瘤(P<0.01);D8S298和D8S1771基因座,肝内转移者的LOH明显高于无肝内转移者(P<0.05)。MSI和AI与HCC临床病理学特点无明显相关性。结论 HCC的8号染色体上存在广泛的微卫星变异,其中以代表肿瘤抑制基因路径的LOH方式在HCC的发生和发展过程中起重要作用,代表错配修复基因路径的MSI的作用次之。特定基因座的LOH与临床和病理学参数有一定的相关性。
Objective To investigate the characteristics of microsatellite mutation on chromosome 8 of hepatocellular carcinoma (HCC) and its relationship with clinicopathological features. Methods The heterozygous deletion (LOH), microsatellite instability (MSI) and allele imbalance (AI) of 10 microsatellites in 56 HCC chromosomes on chromosome 8 were detected by MegaBACE 500 automated DNA analysis system. Mutation characteristics were tested. Results The total frequency of LOH in 10 HCC loci on chromosome 8 was 66.1% (37/56), the frequency of MSI was 12.5% (7/56) and the frequency of AI was 19.6% (11/56) . The highest LOH was 53.5% (23/43) for D8S261, followed by D8S1721 (52.5%) and D8S1771 (52.5%). The frequencies of LOH in D8S277 locus and serum HBsAg positive patients were significantly higher than those in HBsAg negative patients (P <0.01). The frequencies of LOH in D8S261, D8S298 and D8S1733 loci and serum HBsAg negative patients were significantly higher than those in HBsAg positive patients (P <0.01). The LOH rates of tumors> 3 cm in D8S298 and D8S1771 loci were significantly higher than those in <3 cm groups (P <0.05 and P <0.01). At D8S1721 locus, the LOH of non-enveloped or non-enveloped tumors was significantly higher (P <0.01). The LOH of D8S298 and D8S1771 loci and intrahepatic metastasis were significantly higher than those without hepatic metastasis (P <0.05). There was no significant correlation between MSI, AI and clinicopathological features of HCC. Conclusion There is a wide range of microsatellite mutations on chromosome 8 in HCC. LOH, which represents the pathway of tumor suppressor gene, plays an important role in the development and progression of HCC. The role of MSI in mismatch repair gene pathways is second. Specific loci LOH and clinical and pathological parameters have some relevance.